Cyclophosphanum

General characteristics. Structure:

Active ingredient: 200 mg of cyclophosphamide.

Cyclophosphanum has selective antineoplastic activity.

Pharmacological properties:

Pharmacodynamics. Drug concerns to group of the alkylating substances derivative encore - (β-хлорэтил) - amine. Cytostatic effect of drug is implemented directly in tumor cells. At penetration into tumor cells Cyclophosphanum quickly breaks up under the influence of the phosphatases which are contained in them in rather large number (фосфамидаз) with formation of the active component possessing the alkylating action.

Cyclophosphanum has also immunodepressive effect. Like other cytostatics drug suppresses proliferation of the lymphocytic clones participating in an immune response. Thus Cyclophosphanum affects preferential B-lymphocytes.

Pharmacokinetics. Cyclophosphanum gets through a cellular membrane by passive diffusion. At patients with malignant new growths after intravenous administration in a dose of 0,006 — 0,008 g/kg drug quickly gets into fabrics and liquids of an organism. Plasma elimination half-life makes 6,5 h. Cyclophosphanum is distributed in an organism unevenly: collects generally in a spleen, lungs, marrow, a liver and kidneys.

At patients with malignant new growths without functional disturbances of a liver and kidneys about 88% of drug is exposed to metabolism with formation of the alkylated derivatives. In a liver in the presence of a trifosfopiridinnukleotid and molecular oxygen Cyclophosphanum turns into 4 oxycyclophosphamide which of tautomeric form it is formed di - (2 Aether chloratus) - amide and acrolein. Along with it there is an oxidation 4 oxycyclophosphamides in low-toxic 4 oxycyclophosphanum and carboxyphosphamide.

Cyclophosphanum and its metabolites are allocated with urine, at the same time about 20% of the entered amount of drug are removed in not changed look, the rest — in the form of alkyl derivatives. During the first 8 h it is allocated 2/3 from the entered amount of drug. After single intravenous administration active metabolites are defined during 26 — 30 h.

In milk of the feeding women concentration of drug, toxic for marrow of the baby, can be created.

Indications to use:

Drug is used at small-celled cancer of a lung, ovarian cancer, a breast cancer, a reticulosarcoma, a lymphosarcoma, a chronic lymphoid leukosis, an acute lymphoblastoid leukosis, a multiple myeloma, Vilms's tumor, a bone reticulosarcoma, Ewing's tumor, an angiosarcoma.

Route of administration and doses:

The drug is administered intravenously, intramusculary, and also in a cavity. Solutions for injections are prepared just before use on sterile water for injections. The dosing mode — individual.

Apply various schemes of treatment: 1) on 200 mg (3 mg/kg) daily or on 400 mg (6 mg/kg) every other day (intravenously or intramusculary); 2) on 1 g (15 mg/kg) of 1 times in 5 days intravenously; 3) on 2 — 3 g (30 — 45 mg/kg) of 1 times in 2 — 3 weeks intravenously. The course dose at all modes of treatment makes 6 — 14 g. Apply also other schemes of treatment.

At accumulations of liquid as a result of cancer process in belly and pleural cavities in addition to intravenous injections enter into cavities 0,4 — 1,0 g of Cyclophosphanum (at each puncture). The amount of the drug administered intravenously at the same time respectively is reduced.

After the termination of a basic course of treatment the maintenance therapy can be applied by Cyclophosphanum: on 0,1 — 0,2 g of drug 2 times a week intravenously or intramusculary.

As immunodepressive means Cyclophosphanum is applied usually at the rate of 1,0 — 1,5 mg/kg (50 — 100 mg a day), at good tolerance — to 3 — 4 mg/kg.

Use of Cyclophosphanum can cause oppression of a leukopoiesis. It is impossible to begin treatment with drug at quantity of leukocytes ^{less than 3,5x109/l} and quantity of thrombocytes ^{less than 120x109/l}. During treatment it is necessary to conduct blood analyses at least 2 weekly. At decrease in quantity of leukocytes to ^2,5x109/l and thrombocytes to ^100x109/l treatment by Cyclophosphanum stop.

At sharply expressed leukopenia transfuse blood or leukocytic and trombotsitny weight, appoint vitamins and stimulators of a hemopoiesis. Transfusion of the stimulating amounts of blood (100 — 125 ml once a week) is recommended to be carried out during all course of treatment.

Features of use:

At emergence of the following symptoms: a fever, fever, cough or hoarseness, lower back pain or in a side, the painful or complicated urination, bleedings or hemorrhages, a black chair, blood in urine or Calais, it is necessary to consult immediately with the doctor.

Side effects:

At drug use (especially at overdose) often there are nausea and vomiting. For reduction of these phenomena use of antiemetics, and also introduction of a pyridoxine is recommended (intramusculary on 0,05 g). Often (to 90% of cases) in 18 — 20 days after the beginning of use of Cyclophosphanum the partial or full alopecia is observed; hair grow after the termination of administration of drug. Sometimes there are dizziness, deterioration in sight, the dysuric phenomena, a hamaturia. The dysuric phenomena usually pass in 4 — 5 days. Often patients complain of the ostealgia lasting up to 2 — 3 weeks.

At intrapleural administration of drug for 2 — 3 day body temperature can increase, appear cough and thorax pains.

Interaction with other medicines:

Drug increases cardiotoxicity of adriamycin.

At preliminary reception of Allopyrinolum time of semi-removal of Cyclophosphanum from plasma decreases, and the quantity of alkyl metabolites increases. Allopyrinolum strengthens the miyelodepressiya caused by Cyclophosphanum.

The therapeutic effect of Cyclophosphanum is increased by barbiturates, tricyclic antidepressants, theophylline, Chingaminum, hormones of a thyroid gland; reduce (including toxic effect) — glucocorticoids and chloramphenicol.

Contraindications:

The expressed cachexia, anemia, leukopenia, thrombocytopenia, serious illness of heart, liver, kidneys, disease end-stage.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for injections of 200 mg in bottles in packaging No. 1, No. 40.