Gidroksikarbamid

General characteristics. Structure:

Active ingredient: 250 mg of a hydroxycarbamide in 1 capsule.

Pharmacological properties:

Pharmacodynamics. The mechanism of antineoplastic activity is caused by ability of a hydroxycarbamide to inhibit RNK-fosfatreduktazu — one of the main enzymes participating in DNA biosynthesis. Drug quickly breaks DNA synthesis, without exerting impacts on proteinaceous synthesis and synthesis of RNA that results in cytotoxic effect.

Gidroksikarbamid shows specific antineoplastic effect concerning the fast-proliferating transformed cells and has no the expressed cytotoxic effect on slaboproliferiruyushchy or not proliferating normal cells.

The adequate period for assessment of antineoplastic efficiency of drug 6 weeks of therapy are considered. Existence of effect is demonstrated by reduction of the sizes of a tumor or the termination of tumoral growth.

Pharmacokinetics. At intake the hydroxycarbamide is well absorbed from digestive tract and at once gets into fabrics. Passes through a blood-brain barrier. The maximum concentration in a blood plasma (Cmax) is reached in 2 h after administration of drug. In 24 h after reception the content of drug in plasma approaches zero. The elimination half-life (T1/2) makes 3 — 4 h. It is metabolized in a liver with an ureapoiesis and other metabolites. It is allocated preferential with kidneys. About 80% of the drug accepted inside in doses from 7 to 30 mg/kg are removed with urine during 12 h after reception.

Indications to use:

Medicine is applied at acute and a myelosis, a recurrence of an acute lymphoblastoid leukosis at children, an osteomyelofibrosis, an erythremia, a thrombocytosis in the program of a myeloproliferative syndrome, a lymphogranulomatosis, a melanoma, head tumors (except for lips) and necks at impossibility of radical surgical treatment or radiation therapy, metastasises of a breast cancer and a stomach, a colon cancer, a prostate cancer, lung cancer, ovarian cancer, a uterus choriocarcinoma, cancer of a neck of uterus (to increase in efficiency of radiation therapy).

Route of administration and doses:

Medicine is accepted inside, to food. At the request of the patient, or at impossibility of a proglatyvaniye of the capsule, it is possible to pour out its contents in glass with water and to accept immediately, without waiting for full dissolution. Treatment is usually course. There are two main modes of reception - discontinuous (80 mg/kg once inside 1 time in three days) which is often used at the combined treatment of solid tumors (in combination with radiation therapy) and has certain advantages in respect of decrease in toxicity of drug; and also – long (a daily single dose of drug in a dose of 20-30 mg/kg). The recommended schemes of appointment at the long mode of reception: at a myelosis and a thrombocytosis – an initial dose of 20-40 mg/kg/days, further-10-30 mg/kg, at an aggravation – 25-60 mg/kg; at a myelofibrosis – the initial dose of 20 mg/kg supporting – 10 mg/kg; at an erythremia: aggravation of 15-20 mg/kg, maintenance dose of 10 mg/kg; cancer and a melanocarcinoma - 20-30 mg/kg/days.

The adequate period for assessment of antineoplastic efficiency of drug 4-6 weeks of therapy are considered. Existence of effect is demonstrated by reduction of the sizes of a tumor or the termination of tumoral growth; in this case therapy should be continued vaguely long, before emergence of signs of suppression of a marrowy hemopoiesis (a leukopenia (less than 2500 cells/mm3), the thrombocytopenia (less than 100000 cells/mm3) expressed to anemia).

Treatment is usually course. Drug doses, frequency rate of reception and duration of a course of treatment are defined by the doctor individually, according to indications and a condition of the patient.

Use two main modes of administration of drug: discontinuous and long.

At intermittent operation of reception medicine is appointed once in a dose of 80 mg/kg of 1 times in three days. This mode of reception is often used at the combined treatment of solid tumors (in combination with radiation therapy).

At the long mode of reception medicine is appointed daily once in a dose of 20 — 30 mg/kg. The recommended schemes of treatment at the long mode of reception of a hydroxycarbamide the following: at a myelosis and a thrombocytosis the initial dose makes 20 — 40 mg/kg a day, further — 10 — 30 mg/kg, at an exacerbation of a disease the dose is increased to 25 — 60 mg/kg; at a myelofibrosis the initial dose makes 20 mg/kg a day, supporting — 10 mg/kg; at an erythremia in the period of an aggravation the dose makes 15 — 20 mg/kg a day, a maintenance dose — 10 mg/kg; at cancer and a melanocarcinoma drug appoint in a dose 20 — 30 mg/kg a day.

Features of use:

At development of anemia she should be treated, without interrupting a course of treatment with a hydroxycarbamide, by means of the replacing packed red cells transfusions.

The combination with radiation therapy can lead to strengthening of side effects which are connected with a miyelosupressiya, defeat mucous a stomach.

It is necessary to be careful at purpose of a hydroxycarbamide to elderly people and children (reduction of doses is required), and also patients which carried out radiation therapy or treatment by cytostatics earlier. Before an initiation of treatment correction of deep anemia (transfusion of drugs of whole blood) is shown. In the course of treatment it is regularly necessary to control a blood pattern (at least 1 time a month) At decrease in level of leukocytes lower than 2500 cells/mm3 and thrombocytes lower than 100000 cells/mm3 interrupt a course of treatment before emergence of an accurate tendency to normalization of hematologic indicators. Also dynamic control of the level of uric acid, creatinine, transaminases is recommended; at decrease in clearance of creatinine less than 10 ml/min. a dose of drug should be reduced twice. During treatment patients have to use enough liquid.

Side effects:

At reception of medicine anemia, thrombocytopenia, a leukopenia, dispeptic disturbances, stomatitis, fever, headaches, dizziness, a disorientation, hallucinations, intersticial nephrite, a hyperuricemia, increase in level of transaminases in blood serum, an alopecia, an erythema of the person, makulopapulezny rashes are possible. In rare instances diffusion infiltrative damages of lungs and skin allergic reactions can develop.

Interaction with other medicines:

Gidroksikarbamid increases effect of Cytarabinum and weakens action of a 5-ftoruratsil and methotrexate. Increases (mutually) a miyelotoksichnost of the drugs oppressing function of marrow. At joint purpose of drug with uricosuric means the risk of development of a nephropathy increases. In combination with antidepressants, antihistaminic, sedative, somnolent, narcotic drugs and alcohol the hydroxycarbamide strengthens braking of speed of response.

Contraindications:

Contraindications to use of a hydroxycarbamide are hypersensitivity, an acute renal and liver failure, thrombocytopenia (less than 100 000 cells/mm3), a leukopenia (less than 2500 cells/mm3), deep anemia, pregnancy, a lactation.

Issue conditions:

According to the recipe

Packaging:

Capsules of 250 mg in a blister strip packaging No. 10x1, No. 10x3.