Cytarabinum

General characteristics. Structure:

Active ingredient: 100 mg or 1000 mg of Cytarabinum.

Cytarabinum has an antineoplastic, immunodepressive effect.

Pharmacological properties:

Pharmacodynamics. Treats group of antimetabolites of pirimidinovy exchange and has antileukemic activity. Anti-leukemic action of Cytarabinum is caused by braking of proliferation of myeloblasts, lymphoblasts and lymphocytes.

In the course of phosphorylation of Cytarabinum which is most actively proceeding in tumor (leukemic) cells the active metabolite oppressing a DNA polymerase is formed owing to what DNA synthesis is broken.

Pharmacokinetics. After intake it is quickly metabolized, it is preferential deamination (bioavailability less than 20% of the accepted dose).

At intravenous administration after a short phase of distribution (T1/2 makes 10 min.) 80% of the entered Cytarabinum are inactivated to 1-β-D-арабино-фуранозилурацила (T1/2 makes 1 — 3 hour), removed kidneys.

Cytarabinum contacts proteins of plasma (15% of the entered dose). Badly gets through a blood-brain barrier after single intravenous administration, but at continuous infusion concentration in cerebrospinal fluid reaches 40 — 50% of level in blood.

Indications to use:

Cytarabinum is applied at lymphoblastoid and miyeloblastny leukoses, a myelosis, an erythroleukosis, a lymphogranulomatosis, nekhodzhkinsky lymphoma, a marrow dysplasia syndrome.

High-dose therapy by Cytarabinum is applied in induction and consolidation programs at primary acute lymphoblastoid and miyeloblastny leukoses; at the secondary leukoses which arose after the previous cytostatic and/or radiation therapy or as a result of transformation of MDS; at initially resistant forms of acute leukoses; at a resistant recurrence of acute leukoses; at blast crisis of a myelosis; at resistant forms hodzhkinsky and a не-ходжкинских of lymphoma of high degree of a zlokachestvennost.

Route of administration and doses:

Cytarabinum is entered intravenously, subcutaneously or intratekalno. Just before the use Cytarabinum is dissolved in isotonic (0,9%) solution of sodium of chloride or in water for injections (from calculation: for intravenous administration — 100 mg of Cytarabinum in 400 ml of solvent; for hypodermic and intrathecal introduction — 100 mg of Cytarabinum in 1 ml of solvent).

Intravenously Cytarabinum enter in a dose 100 mg/sq.m a day: in the form of two drop infusions for 3 hours with an interval of 10 hours or it is continuous during 24 h. At patients of advanced age or with the lowered reserves of a hemopoiesis apply smaller doses of drug — 50 — 75 mg/sq.m a day.

Carry out also "high-dose" therapy by Cytarabinum: on 3 g/m2 in the form of infusion within 75 min. each 12 h within 1 — 6 days.

Subcutaneously Cytarabinum enter in a daily dose 20 mg/sq.m, 2 — 3 times a day, daily, within 3 — 10 days (no more).

Intratekalno for prevention of neuroleukoses the drug is administered by each 3 days within 2 weeks, in a dose of 20 mg/sq.m. For definition of individual portability of drug in these cases perhaps gradual increase in a single dose from 3 mg/sq.m to 20 mg/sq.m. In total treat 4 — 7 courses of treatment between courses make 10 — 14 days and more.

The repeated course of treatment by Cytarabinum is carried out after recovery of a hemogenesis. High-dose therapy by Cytarabinum has to be performed by the doctors and the prepared medical staff having experience of carrying out chemotherapy of oncohematological diseases in specialized clinics (departments).

When carrying out the combined chemotherapy of a dose of Cytarabinum reduce.

Cytarabinum is applied independently or in a combination with other cytostatic means (Cyclophosphanum, Vincristinum, thioguanine, L-asparaginase, рубомицин, Carminomycinum, флударабин) and Prednisolonum.

1000 mg: for fractional introduction in the form of drop infusions just before the use contents of a bottle are dissolved in 100 - 250 ml isotonic (0,9%) chloride sodium solution, or water for injections, or by 5% of solution of a dextrose in isotonic (0,9%) solution of sodium of chloride or in water for injections, or Ringer's solution. Duration of infusions is from 30 minutes till 2 o'clock. When performing "high-dose" therapy by Cytarabinum duration of infusions should not exceed 2 hours. For long infusions just before the use contents of a bottle are dissolved in 500 - 1000 ml isotonic (0,9%) chloride sodium solution, or water for injections, or by 5% of solution of a dextrose in isotonic (0,9%) solution of sodium of chloride or in water for injections, or Ringer's solution. Concentration of Cytarabinum and rate of administering is defined individually. For hypodermic and intrathecal introduction just before the use of 0,5 or 1,0 g of Cytarabinum dissolve in 10 ml isotonic (0,9%) solution of sodium of chloride or in water for injections, final concentration of drug will make 50 mg/ml and 100 mg/ml respectively (Attention! For intrathecal introduction it is impossible to use the solvents containing benzyl alcohol). Intravenously Cytarabinum enter in a dose 100 mg/m a day: in the form of two drop infusions for 2 hours with an interval of 10 hours or it is continuous during 24 h. At patients of advanced age or with the lowered reserves of a hemopoiesis apply smaller doses of drug 50 - 75 mg/sq.m a day. Course dose of 500-1000 mg. The break between courses makes 7-14 days.

Carry out also "high-dose" therapy by Cytarabinum: on 3 g/m2 in the form of infusions within 75 min. each 12 h within 1-6 days. Subcutaneously Cytarabinum enter in a daily dose 20 mg/m, 2 - 3 times a day, daily, within 3-10 days (no more).

Intratekalno for prevention of neuroleukoses the drug is administered by each 3 days within 2 weeks, in a dose of 20 mg/sq.m. For definition of individual portability of drug in these cases perhaps gradual increase in a single dose from 3 mg/sq.m to 20 mg/sq.m. In total conduct 4 - 7 courses of treatment; intervals between courses make 10-14 days and more. The repeated course of treatment by Cytarabinum is carried out after recovery of a hemogenesis.

High-dose therapy by Cytarabinum has to be performed by the doctors and the prepared medical staff having experience of carrying out chemotherapy of oncohematological diseases in specialized clinics (departments). When carrying out the combined chemotherapy of a dose of Cytarabinum reduce. Cytarabinum is applied independently or in a combination with other cytostatic means (thioguanine, doxorubicine, даунорубицин, etc.) and Prednisolonum.

Features of use:

Treatment by Cytarabinum is performed under control of quantity of leukocytes in peripheral blood (daily or every other day) and marrow (before and after each course of therapy).

At number of thrombocytes less than 50000/mm3 and/or polymorphonuclear granulocytes — lower than 1000/mm3 treatment is stopped.

With care apply Cytarabinum at patients with infiltration of marrow tumor cells.

It is not recommended to apply Cytarabinum at patients with chicken pox, with the surrounding herpes.

It is necessary at least once a week to control a functional condition of a liver, prior to the beginning of and after the termination of a course of therapy to carry out by Cytarabinum control of secretory function of kidneys.

When carrying out programs of high-dose therapy by Cytarabinum daily monitoring of the general blood test and biochemical indicators is necessary. At patients with an initial hyperleukocytosis or big mass of a tumor (at lymphoma) control of level of uric acid in blood is necessary.

In pilot studies teratogenic, embriotoksichesky and mutagen action of Cytarabinum is established.

Side effects:

Oppression of function of marrow, leukopenia, thrombocytopenia, megaloblastny anemia, thrombophlebitis, bleedings in a GIT, stomatitis, an esophagitis, nausea, vomiting, diarrhea, disturbances of activity of TsNS, function of a liver, a hyperuricemia, a nephropathy, a panniculitis, a fluid lungs, a diffusion intersticial pneumonitis, a headache (after intrathecal introductions), an itch, a hair loss, "a tsitarabinovy syndrome" — fever, a mialgiya, bone and retrosternal pains, makulopapulezny rash, conjunctivitis, alarm.

At high-dose therapy by Cytarabinum — a miyelosupressiya: thrombocytopenia, leukopenia, anemia; мегалобластоз; immunosuppression, fever, alopecia, allergic reactions, nausea, vomiting, diarrhea, stomatitis, abdominal pains, loss of appetite, abnormal liver function, mialgiya, thrombophlebitises. As a rule, the specified symptoms stop after the termination of a course of treatment.

At use of high doses of Cytarabinum development deeper is possible and long, than at introduction in standard dosages, miyelosupressiya (the average duration of the period of an agranulocytosis and thrombocytopenia — 28 — 30 days) Are possible the side effects caused by increase in concentration of drug in the lacrimal liquid (burning in eyes, dacryagogue, a photophobia, complaints to decrease in sight (in the preventive purposes it is necessary to appoint corticosteroid eye drops)) and in liquor (cerebellar dysfunctions, an ataxy and drowsiness). Ophthalmologic and neurologic symptoms stop in several days after the end of therapy by Cytarabinum. In 6 — 12 hours after use of Cytarabinum "the tsitarabinovy syndrome" can develop.

In case of need at development of the expressed by-effects glucocorticoids in sredneterapevtichesky dosages for carrying out a course of treatment Cytarabinum are appointed.

Interaction with other medicines:

At simultaneous use with digoxin decrease in Css of digoxin and its removal is noted by kidneys (careful control of content of digoxin is required). Css of digitoxin does not change.

At combined use with other antineoplastic medicines, performing radiation therapy perhaps mutual strengthening of toxicity and immunodepressive effects. Immunodepressants (azathioprimas, хлорамбукол, GKS, cyclophosphamide, cyclosporine, Mercaptopurinum, такролимус) increase risk of development of infectious complications.

Vaccination with use of vaccines with the killed viruses (because of decrease in protective mechanisms antibody formation is lowered) and with live viruses (increase in side effects, decrease in antibody formation) is inefficient.

Pharmaceutical it is incompatible with heparin, insulin, a methotrexate, ftoruratsily, naftitsilliny, Oxacillinum, benzylpenicillin, Methylprednisolonum.

Contraindications:

Hypersensitivity, marrow aplasia, insufficiency of function of a liver and kidneys, acute infectious diseases, beam or chemotherapy (including in the anamnesis), pregnancy and feeding by a breast (for the period of treatment it is necessary to stop breastfeeding).

Restrictions to use: beam or chemotherapy (including in the anamnesis).

Overdose:

Symptoms. Intravenous drop administration of 4,5 g/m2 each 12 h for 12 days leads to an irreversible damage of TsNS, incompatible with life.

Treatment: symptomatic, the specific antidote does not exist.

Issue conditions:

According to the recipe

Packaging:

The powder lyophilized for preparation of solution for injections of 1000 mg in bottles in packaging No. 1, No. 40.

The powder lyophilized for preparation of solution for injections of 100 mg in ampoules in packaging No. 5.