Gidrea

Gidrea – antineoplastic drug.

Form of release and structure

The Gidre is released in the form of capsules: gelatinous firm, opaque, the size No. 0, with a text of black color "BMS 303", the case – opaque, light pink color, a lid – opaque, green color; capsule contents – the white condensed weight or powder (on 100 pieces in dark glass bottles, on 1 bottle in a cardboard pack; on 10 pieces in blisters, on 2 blisters in a cardboard pack).

Is a part of 1 capsule:

• Active ingredient: a hydroxycarbamide – 500 mg;
• Auxiliary components: monohydrate of lactose – 42,2 mg, citric acid – 12,8 mg, magnesium stearate – 9 mg, hydrosodium phosphate – 36 mg.

Structure of a cover of the capsule: titanium dioxide – 2,016 mg, gelatin – 93,743 mg, dye iron oxide yellow – 0,110 mg, dye iron oxide red – 0,115 mg, dye FD&C indigo carmine of blue 2 – 0,017 mg.

The structure blackened: black iron oxide, shellac, propylene glycol, N-butyl alcohol, isopropyl alcohol, industrial metilirovanny alcohol, the purified water.

Indications to use

• Malignant tumors of the head and neck, except lip cancer (along with performing radiation therapy);
• Osler's disease (erythremia);
• Myelosis;
• Osteomyelofibrosis;
• Essential trombotsitemiya;
• Cancer of a neck of uterus (along with performing radiation therapy);
• Melanoma.

Contraindications

Absolute:

• Thrombocytopenia lower than 100 000/mkl, a leukopenia is lower 2500/mkl;
• Pregnancy and period of a lactation;
• Children's age (efficiency and safety of use of Gidrea for this age group of patients are not established);
• Hypersensitivity to drug components.

Relative (Gidrea appoint with care in the presence of the following diseases / states):

• Glyukozo-galaktozny malabsorption, lactose intolerance, deficit of lactase;
• Heavy anemia (it is necessary to compensate prior to therapy);
• Renal and/or liver failure;
• State after postponed himio-or radiotheraphy (because of probability of an aggravation of a beam erythema, development of a miyelosupressiya).

Route of administration and dosage

The Gidre is accepted inside. In the presence of difficulties of swallowing it is possible to open the capsule, to pour out contents in glass with water and to drink immediately. At the same time some of water insoluble auxiliary components can remain on the surface of solution.

The doctor defines the dosing mode individually, based on data of special literature.

During therapy it is necessary to accept liquid in rather large number.

Depending on indications, Gidrea usually appoint as follows:

• Resistant myelosis: once a day on 20-30 mg/kg daily (continuous therapy). Assessment of efficiency of Gidrea should be carried out in 1,5 months of treatment. In the presence of the acceptable clinical answer, therapy it is possible to spend beyond all bounds long time. Treatment is stopped if the number of leukocytes makes ^{less than 2500/mm3} or the maintenance of thrombocytes – ^{less than 100 000/mm3}. 3 days later blood test carry out repeatedly. Therapy can be resumed after increase in number of erythrocytes and leukocytes up to acceptable. Recovery, as a rule, happens quickly enough, otherwise at simultaneous use of Gidrea to radiation therapy, the last can be also suspended. Anemia, even heavy, usually does not lead to interruption of a course of treatment on condition of performing adequate therapy (a packed red cells transfusion);
• Osler's disease: use of Gidrea is begun with 15-20 mg/kg a day. The dose is established individually, at the same time it is desirable to support number of thrombocytes – lower than 400 000/mkl, a hematocrit – at the level of lower than 45%. In most cases it works well at constant use of a hydroxycarbamide in a daily dose of 500-1000 mg;
• Essential trombotsitemiya: The Gidrea appoint in an initial dose 15 mg/kg a day. Then the dose is selected so that to support number of thrombocytes at the level of lower than 600 000/mkl, without leading at the same time to decrease in number of leukocytes is lower 4000/mkl. At solid tumors and a melanoma carry out discontinuous (once a day on 80 mg/kg each three days; 6-7 doses) or continuous (daily for 3 weeks on 20-30 mg/kg once a day) therapy;
• Carcinoma of a neck of uterus, carcinoma of the head and neck: once a day on 80 mg/kg, each three days in a combination with performing radiation therapy. The Gidre is appointed not less than in 7 days prior to the beginning of a course of radiation therapy and do not interrupt administration of drug during all course. At absence at the patient of heavy or unusual toxic reactions after the end of radiation therapy use of drug should be continued during unlimited time under strict medical control.

At patients with functional disturbances of a liver it is necessary to carry out careful monitoring of indicators of blood. This group patients has no data on need of change of doses.

At purpose of Gidrea patients with functional disturbances of kidneys need to carry out dose adjustment. At clearance of creatinine to 60 ml a minute drug is, as a rule, appointed in a dose of 15 mg/kg. Patients with an end-stage of a renal failure of Gidrea should apply in the same dose twice, with a break in 7 days: the first time – upon termination of a four-hour session of a hemodialysis, the second – before holding a session of a hemodialysis.

Elderly patients are recommended to appoint drug in the doses which are not exceeding 60 mg/kg a day.

Side effects

• Nervous system: with an unknown frequency – drowsiness, dizziness, a disorientation, a headache, spasms, hallucinations, peripheral neuropathy (at the HIV-positive patients who are at the same time receiving anti-retrovirus therapy, for example, ставудин and диданозин), increased fatigue;
• Urinary system: with an unknown frequency – intersticial nephrite, an ischuria, increase in content of uric acid in blood serum, the maintenance of an urea nitrogen and creatinine in a blood plasma; seldom – a dysuria;
• Respiratory system: with an unknown frequency – diffusion infiltration of lungs, a pneumosclerosis, an asthma;
• Skin and skin appendages: with an unknown frequency – a skin vasculitis, makulezno-papular rashes, ulcerations on skin, a peripheral erythema and an erythema of the person, dermatomiozitopodobny changes and exfoliation of skin, an erythema, a hyperpegmentation, a peeling, papules of violet color, an atrophy of nails and skin, skin toxic vasculites (including gangrene and vaskulitny ulcerations); seldom – a carcinoma cutaneum, an alopecia;
• Digestive organs: with an unknown frequency – a hepatotoxic, pancreatitis (in certain cases with a lethal outcome) (at the HIV-positive patients who are at the same time receiving anti-retrovirus therapy, for example, ставудин and диданозин), dyspepsia, stomatitis, diarrhea, anorexia, vomiting, nausea, a lock, mukozit, an ulceration of a mucous membrane of digestive tract, irritation of a mucous membrane of a stomach, increase in concentration of bilirubin in plasma and activity of liver enzymes;
• Bodies of a hemopoiesis: with an unknown frequency – suppression of function of marrow (anemia, a leukopenia, thrombocytopenia);
• Infections: with an unknown frequency – gangrene;
• Others: with an unknown frequency – an adynamy, skin allergic reactions, a fever, a febricula, fever, increase in the blood sedimentation rate (BSR); seldom – an asthma, diffusion infiltration of lungs.

Cases of development of a hepatotoxic and pancreatitis (with a possible lethal outcome), and also heavy peripheral neuropathy were noted at sick HIV which accepted Gidrea along with anti-retrovirus medicines, in particular, диданозин jointly with stavudiny or without it.

The most private disturbances observed at combined use of Gidrea and radiation therapy same, as well as when performing monotherapy – oppression of function of marrow (anemia, a leukopenia) and irritation of a mucous membrane of a stomach. Besides, reception of a hydroxycarbamide can lead to strengthening of some side effects which are usually observed at radiation therapy (mukozit, discomfort in a stomach).

Special instructions

The Gidre can be applied only under observation of the doctor having experience of performing antineoplastic therapy.

Before each course and periodically during therapy it is necessary to control functions of marrow, a liver and kidneys. Definition of leukocytes, thrombocytes and hemoglobin has to be carried out at least 1 time in 7 days throughout the entire period of use of Gidrea. Therapy appoint only in cases if the maintenance of leukocytes is higher 2500/mkl, and thrombocytes – 100 000/mkl. At decrease in their level therapy is interrupted before their normalization.

Prior to treatment anemia in a severe form should be compensated.

During use of Gidrea the miyelosupressiya, most often – a leukopenia can develop. Anemia and thrombocytopenia develop less often, and in absolutely exceptional cases – without the previous leukopenia. Development of a miyelosupressiya in patients after recently carried out chemotherapy by other drugs or radiation therapy is the most probable.

After carried out in recent time beam or chemotherapy of Gidrea it is necessary to apply with care that is connected with probability of an aggravation of a post-radiation erythema and strengthening of expressiveness of side effects (a digestive tract ultseration, dyspepsia, a marrow aplasia). At development of heavy disturbances from digestive organs, such as vomiting, nausea, anorexia, therapy is stopped, as a rule.

At pains and discomfort at emergence of a mukozit in the field of radiation local anesthetics and analgetics for oral administration are usually appointed. In hard cases treatment is temporarily stopped, at very heavy current temporarily cancel the accompanying radiation therapy.

The Gidrea can slow down clearance of iron of plasma and lower iron utilization speed erythrocytes, but it does not exert impact on time of life of erythrocytes.

At early stages of use of Gidrea the moderate megaloblastichesky erythrogenesis is often observed. Morphological changes usually remind pernicious anemia, but they are not connected with deficit of folic acid or B12 vitamin. Because the macrocytosis can mask a lack of folic acid, it is necessary to consider a question of its preventive appointment to the patient.

Against the background of myeloproliferative diseases during use of Gidrea skin toxic vasculites, including gangrene and vaskulitny ulcerations were observed. It was most often reported about toxic vasculites at the patients receiving in the past or receiving now interferon. Administration of drug when progressing vaskulitny ulcerations needs to be stopped.

At long use of Gidrea for patients with myeloproliferative diseases, such as trombotsitemiya and Osler's disease, cases of secondary leukoses were noted. The reason of development of a secondary leukosis (reception of a hydroxycarbamide or a basic disease) is unknown. Also long therapy can lead to development of a carcinoma cutaneum therefore during therapy it is recommended to protect skin from a sunlight and to systematically carry out self-checking of its state. At planned visits of the doctor it is necessary to control a condition of integuments of the patient for identification of possible malignant changes.

As Gidrea has cytotoxic effect, when opening capsules it is necessary to be careful, and also it is necessary to avoid inhalation of drug or hit of powder on mucous membranes and skin.

The Gidrea can lead to development of dizziness and other undesirable phenomena from a nervous system that needs to be considered at control of motor transport.

Medicinal interaction

At simultaneous use of Gidrea with some medicines there can be following effects:

• Other myelosuppressive drugs or radiation therapy: increase in extent of suppression of function of marrow or risk of development of other side effects;
• Cytarabinum: increase in its cytotoxic effect;
• Uricosuric means: increase in risk of development of a nephropathy.

If when performing the combined treatment there is heavy dyspepsia, nausea, anorexia or vomiting, usually they can be stopped interruption of reception of Gidrea.

Mukozit (discomfort and morbidity of mucous membranes in the place of radiation) it is possible to facilitate local anesthetics and analgeziruyushchy drugs (inside). At a heavy mukozit use of Gidrea is temporarily interrupted; in very hard cases – stop radiation therapy.

Drug is capable to increase the content of uric acid in blood serum that can demand correction of a dose of the medicines increasing removal from an organism of uric acid.

As a result of interaction of a hydroxycarbamide and enzymes (uricase, urease, a lactate dehydrogenase) during use of Gidrea cases of emergence of false positive results of analyses when determining uric acid, urea and lactic acid were noted.

Terms and storage conditions

To store in protected from light, the place, unavailable to children, at a temperature of 15-25 °C.

Period of validity – 5 years.