Gidroksikarbamid

General characteristics. Structure:

Active ingredient: 500 mg of a hydroxycarbamide in 1 capsule.

Pharmacological properties:

Pharmacodynamics. S-fazospetsifichnym is means, inhibits a ribonukleotidreduktaza, quickly breaking DNA synthesis, not influencing synthesis of RNA and protein that results in cytotoxic effect. Suppresses activity of polymerases, process of recovery of DNA after potentially lethal damages by radiation or chemical agents is as a result broken. This mechanism of action of a hydroxycarbamide allows to use it as a radio sensitizer.

The adequate period for assessment of antineoplastic efficiency of a hydroxycarbamide 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.

Significantly increases efficiency of radiation therapy at brain tumors, cancer of a neck of uterus.

Use at treatment of psoriasis (mainly a pustular form), Sneddon's diseases — Wilkinson, a gangrenous pyodermatosis, psoriasis erythroses, a sickemia is possible.

In various test systems gene toxicity of a hydroxycarbamide is revealed. Cases of developing of a secondary leukosis were noted at the patients receiving drug a long time at treatment of myeloproliferative disturbances (an Osler's disease, a trombotsitemiya).

In animal experiments teratogenic and cancerogenic action is revealed; influences fertility; it is shown that the hydroxycarbamide passes through a placenta and has embriotoksichesky effect. However adequate and strictly controlled researches at pregnant women were not conducted. In in vitro experiments the hydroxycarbamide had mutagen effect on cells of bacteria, mushrooms, protozoa and mammals; the klastogennost of a hydroxycarbamide is confirmed in in vitro experiments (on cells of hamsters and lymphoblasts of the person) and in vivo (the test of exchange of sister chromatids at rodents, micronuclear test at mice).

Pharmacokinetics. After intake it is well absorbed from a GIT and at once gets into fabrics, does not kumulirut in an organism. In cerebrospinal fluid there are 10–20%, in ascitic — 15–50% of concentration in plasma. Biocomprehensibility averages (108±36) %. Passes through GEB. Cmax is reached in 2 h after reception and averages 22,9–65,6 mg/l. In 24 h the content in plasma approaches zero. T1/2 is 3–4 h. It is partially metabolized in a liver and kidneys. 50% in not changed look and in small amounts in the form of urea are allocated preferential with kidneys (at oral administration or in introduction from 7 to 30 mg/kg of 80% of a dose it is removed with urine during 12 h). It is removed also through respiratory tracts in the form of dioxide carbon.

Is exposed to elimination during dialysis.

Indications to use:

Myelosis, osteomyelofibrosis, erythremia, essential trombotsitemiya, melanoma; malignant tumors of the head and neck (except for lip cancer) at impossibility of radical surgical treatment or radiation therapy; cancer of a neck of uterus (in a combination with radiation therapy).

Route of administration and doses:

Inside, in need of (impossibility of a proglatyvaniye of capsules) contents of capsules are poured out in glass with water and immediately accepted. Apply as in the monotherapy mode (palliative chemotherapy of the III-IV line), and in a combination with other cytostatic drugs or radiation therapy. The mode of dosing is defined individually.

In the monotherapy mode (including for the purpose of a radio sensitization): 20–30 mg/kg daily during 3 weeks, a daily dose — 2000 mg; or 80 mg/kg 1 разв 3 days (6–7 doses). If after 4 weeks of therapy the expressed progressing of a disease continues to be observed, treatment is stopped. For a radio sensitization administration of drug in 7 days prior to radiation therapy is recommended.

At sufficient efficiency treatment is carried out during unlimited time. An average maintenance dose — 500–2000 mg. Development of anemia does not demand interruption of a course of treatment on condition of adequate therapy.

Features of use:

Use at pregnancy and feeding by a breast. Contraindicated at pregnancy. For the period of treatment it is necessary to stop breastfeeding.

Use of a hydroxycarbamide is carried out under strict medical control.

With care appoint to elderly people and children (reduction of doses is required), to patients to whom it was carried out beam or chemotherapy, the patient with a tumor of kidneys, at a renal and liver failure earlier. Before an initiation of treatment correction of deep anemia (transfusion of drugs of whole blood) is shown.

Before and during treatment (at least 1 time a week) regular blood test is necessary; at reduction of number of leukocytes lower than 2,5·10 9/l and thrombocytes lower than 100·10 9/l course of treatment is interrupted 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 Cl of creatinine less than 10 ml/min. a dose уменьшаютв 2 times.

Dental interventions should be completed whenever possible prior to therapy or to postpone until normalization of a picture of blood (possibly increase in risk of microbic infections, delay of processes of healing, bleeding of gums). During treatment to be careful when using toothbrushes, threads or toothpicks.

During treatment inoculations of virus vaccines are not recommended, it is necessary to avoid contact with the people who received a vaccine against poliomyelitis with sick bacterial infections. It is not necessary to apply live virus vaccines at patients with a leukosis in a remission stage at least within 3 months after a last year of chemotherapy. Immunization by a peroral vaccine against poliomyelitis of the people who are in close contact with such patient, especially family members should be delayed.

Emergence of signs of oppression of function of marrow, unusual bleedings or hemorrhages, black tar-like chair, blood in urine or Calais or dot red spots on skin demand immediate consultation of the doctor.

To be careful in order to avoid accidental cuts sharp objects (a safety razor, scissors), to avoid occupations contact sports or other situations at which hemorrhage or injuries are possible.

In the course of treatment consumption of enough liquid and the subsequent strengthening of a diuresis is important for ensuring removal of uric acid.

To be careful at a combination therapy; it is necessary to accept each drug in due time.

At absence at sick clinical effect in 6 weeks of treatment use of drug should be stopped; in case of efficiency of therapy administration of drug it is possible to continue unlimited time.

Patients with the developed leukopenia should be observed carefully for identification of signs of developing of an infection, if necessary — to appoint antibiotics. The patient with a neutropenia at fervescence antibiotics of a broad spectrum of activity are appointed empirically before obtaining results of bacteriological researches and the corresponding diagnostic tests.

At patients with the thrombocytopenia which developed as a result of use of a hydroxycarbamide it is recommended to observe special precautionary measures (restriction of frequency of venipunctures, refusal of injections in oil, regular survey of places in/in administrations of drugs, skin and mucous membranes, refusal of the use of acetylsalicylic acid, etc.).

During treatment it is not recommended to manage the vehicle and to perform the work connected with the increased concentration of attention.

The combination with radiation therapy can lead to strengthening of expressiveness of side effects (a marrow aplasia, dyspepsia and development of a canker of a GIT).

During treatment use of contraceptives is recommended.

Side effects:

From a nervous system and sense bodys: headache, dizziness, increased fatigue, drowsiness, spasms, disorientation; seldom — spasms, hallucinations.

From cardiovascular system and blood: leukopenia, anemia, thrombocytopenia.

From respiratory system: fluid lungs, pulmonary infiltrate.

From bodies of a GIT: stomatitis, bleeding of gums, anorexia, nausea, vomiting, diarrhea/lock, ulceration of a mucous membrane of a GIT, increase in activity of enzymes of a liver.

From urinogenital system: intersticial nephrite, uraemia, a hyperuricemia, the painful or complicated urination, fertility disturbance (an azoospermism, the termination of periods).

From integuments: makulo-papular rashes, itch, dermahemia of the person, hair loss, trophic ulcers, skin hyperpegmentation, aggravation of a post-beam erythema, fragility of nails.

Others: fervescence, fever, febricula, increase in SOE.

Interaction with other medicines:

Against the background of uricosuric means the risk of development of a nephropathy increases. The drugs causing pathological changes of blood strengthen a leukopenia and/or thrombocytopenia if these drugs have the same effect, as well as a hydroxycarbamide, concerning leukocytes and thrombocytes.

Other drugs causing oppression of function of marrow or radiation therapy exponentiate effect and is additive oppress function of marrow.

At introduction of live virus vaccines strengthening of side effects or decrease in development of antibodies are possible; the inactivated vaccines — decrease in development of antiviral antibodies.

Contraindications:

Hypersensitivity, thrombocytopenia (less than 100·10 9/l), the expressed leukopenia (less than 2,5·10 9/l), pregnancy, breastfeeding.

Restrictions to use. Renal and/or liver failure; anemia (it has to be eliminated before an initiation of treatment); virus (including chicken pox, shingles), fungal and bacterial infections.

Overdose:

Symptoms: at purpose of high doses of drug (above, than 60 mg/kg/days) undesirable effects, including with heavy dysfunctions of marrow can amplify.

Treatment: symptomatic, preventive anti-infectious therapy, transfusion of components of blood according to indications. The specific antidote is unknown.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Capsules of 500 mg. On 10 or 20 capsules in each blister, on three, six or ten blisters together with the application instruction in cardboard packaging.