Hydroxycarbamide Medac, 500mg capsules, 100pcs

Composition

Active ingredients:

hydroxycarbamide 500 mg.

Auxiliary substances:

lactose,

calcium citrate,

sodium citrate,

magnesium stearate.

Shell composition:

gelatin, titanium dioxide.

Pharmacological action

Pharmacodynamics

Hydroxycarbamide is a phase-specific cytostatic drug (an antimetabolite, according to some sources – an alkylating agent) that acts in the S phase of the cell cycle.

It blocks the growth of cells in the Gl-S interphase, which is essential for simultaneous radiation therapy, since there is a synergistic sensitivity of tumor cells in the Gl phase to radiation. By enhancing the action of the RNA reductase inhibitor, ribonucleoside diphosphate reductase, it causes suppression of DNA synthesis. The drug does not affect the synthesis of RNA and protein.

Pharmacokinetics

After oral use, it is rapidly absorbed from the gastrointestinal tract. Cmax of the drug in blood plasma is reached 1-4 hours after use. Food intake does not affect the absorption of the drug. It is rapidly distributed throughout the body’s tissues, penetrates through the blood-brain barrier.

In the cerebrospinal fluid,10-20% is determined, in the ascitic fluid-15-50% of the concentration in the blood plasma. T1 / 2 – 3-4 h. Partially metabolized in the liver and kidneys. 80% of hydroxyurea is excreted in the urine within 12 hours, while 50% is unchanged and in small amounts in the form of urea. The drug is also excreted through the respiratory tract in the form of carbon dioxide. It is not detected in plasma after 24 hours.

Indications

• Chronic myeloid leukemia;
• true polycythemia (erythremia);
• essential thrombocythemia;
• osteomyelofibrosis;
• melanoma;
• malignant tumors of the head and neck, except for lip cancer (in combination with radiation therapy);
• cervical cancer (in combination with radiation therapy).

Use during pregnancy and lactation

It is contraindicated during pregnancy and lactation.

Contraindications

• Hypersensitivity to hydroxycarbamide or any other excipient included in the preparation;
• pregnancy and lactation;
• leukopenia below 2500 / mcl, thrombocytopenia below 100,000/mcl.

With caution: hepatic and / or renal insufficiency, anemia (should be corrected before starting treatment).

Side effects

Hematopoietic disorders: leukopenia, anemia, thrombocytopenia.

From the digestive system: stomatitis, anorexia, nausea, vomiting, diarrhea or constipation, ulceration of the gastrointestinal mucosa. Increased activity of liver enzymes.

From the skin and skin appendages: macular-papular rashes, facial erythema and peripheral erythema, dermato-myositic skin changes. In some cases, as a result of daily use of the drug for several years, patients experienced hyperpigmentation, erythema, atrophy of the skin and nails, peeling, purple papules. In rare cases, there is alopecia, skin cancer.

Nervous system disorders: headache, dizziness, fatigue, drowsiness, disorientation; rarely-hallucinations and convulsions.

From the urinary system: increased uric acid, blood urea nitrogen and creatinine in blood plasma, urinary retention, interstitial nephritis. In rare cases, dysuria is noted.

Other: chills, general malaise, increased ESR, allergic skin reactions. In rare cases, acute pulmonary reactions associated with the use of the drug have been reported; diffuse lung infiltration, fever and shortness of breath.

Interaction

When the drug is used concomitantly with other myelosuppressive drugs or radiation therapy, the degree of suppression of bone marrow functions or the development of other side effects may increase.

The drug may increase the uric acid content in the blood, so it may be necessary to adjust the dose of drugs that increase the excretion of uric acid from the body. Uricosuric drugs increase the risk of developing nephropathy.

How to take, course of use and dosage

When choosing the regimen and doses in each individual case, you should be guided by the data of the specialized literature.

The drug is used inside.

If swallowing is difficult, you can open the capsule, dissolve the contents in a glass of water and drink it whole. At the same time, some water-insoluble excipients can float on the surface of the solution.

During treatment with the drug, a sufficiently large amount of liquid should be taken.

Solid tumors

• 80 mg / kg once a day every three days (6-7 doses).
• 20-30 mg/kg daily for 3 weeks.

Head and neck carcinoma, cervical

carcinoma 80 mg / kg once a day, every third day in combination with radiation therapy.

Treatment with the drug begins at least 7 days before the start of radiation therapy and continues during radiation therapy. After radiation therapy, the drug continues to be taken indefinitely with strict monitoring of the patient and in the absence of unusual or severe toxicity reactions.

Resistant chronic myeloid leukemia

Continuous therapy. From 20 to 30 mg / kg daily once a day.

Evaluation of the effectiveness of the drug is carried out after 6 weeks of treatment. With severe clinical remission, treatment can be continued indefinitely. Treatment should be suspended if the white blood cell count is less than 2500/mm3, and the platelet count is less than 100000/mm3. After 3 days, the blood test is repeated. Treatment is resumed when the content of white blood cells and red blood cells begins to increase markedly.

True polycythemia

Treatment begins with a daily dose of 15-20 mg / kg. The dose is set individually, trying to maintain the hematocrit at a level below 45%, and the number of platelets-below 400,000/µl. In most patients, it is possible to achieve these indicators by constantly using hydroxycarbamide in a daily dose of 500 to 1000 mg.

Essential thrombocythemia

Usually, the drug is prescribed at an initial daily dose of 15 mg / kg; then a dose is selected that maintains the platelet count at a level below 600,000 / µl, without leading to a decrease in the number of white blood cells below 4000/µl.

Overdose

When using the drug in doses several times higher than recommended, patients develop signs of acute dermatological toxicity: soreness, purple erythema, edema followed by peeling of the palms of the hands and feet, intense generalized hyperpigmentation of the skin and severe acute stomatitis.

The specific antidote is not known. Treatment is symptomatic.

Special instructions

Treatment with the drug should be carried out under the supervision of a doctor. Before and periodically during treatment with the drug, it is necessary to check the functions of the bone marrow, kidneys and liver. Determination of hemoglobin, white blood cells and platelets should be carried out at least once a week during the entire period of treatment with the drug. If the white blood cell count is less than 2500 / µl or platelet count is less than 100000/µl, treatment should be suspended until their content is restored to normal.

The drug has a cytotoxic effect, so care should be taken when opening capsules and avoid getting capsule powder on the skin, mucous membranes or inhaling the drug. If the contents of the capsule are accidentally spilled, immediately collect the powder with a napkin in a plastic bag, tie it and throw it away.

Anemia is not a contraindication for treatment with the drug. Severe anemia should be compensated for before treatment with the drug.

During treatment with the drug, myelosuppression may develop, mainly leukopenia. Thrombocytopenia and anemia develop less frequently and very rarely without prior leukopenia. Anemia, even in severe form, is stopped without interruption of treatment. Myelosuppression is most likely to occur in patients who have recently undergone previous intensive radiation therapy or chemotherapy with other medications. After recent intensive radiation therapy, the drug should be used with caution due to possible exacerbation of post-radiation erythema and increased severity of side effects (bone marrow aplasia, dyspepsia and ulceration of the gastrointestinal tract).

In the early stages of treatment with the drug, moderate megaloblastic erythropoiesis is often observed. Morphological changes are similar to malignant anemia, but they are not associated with vitamin B12 or folic acid deficiency.

The drug may reduce the clearance of iron from blood plasma and reduce the efficiency of iron utilization by red blood cells, but it does not affect the life of red blood cells.

During treatment, patients should consume a sufficient amount of fluids. The drug should be used with caution in patients with impaired renal and hepatic function. It may be necessary to reduce the dose of the drug.

Form of production

Capsules

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf life

4 years

Active ingredient

Hydroxycarbamide

Conditions of release from pharmacies

By prescription

Dosage form

Capsules