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Active ingredients
Hydroxycarbamide
Release form
Capsules
Composition
Active ingredient: Hydroxycarbamide (Hydroxycarbamidum) Concentration of the active substance (mg): 500
Pharmacological effect
Antitumor agent. The proposed mechanism of action is the inhibition of DNA synthesis. No effect on protein and RNA synthesis.
Pharmacokinetics
After ingestion is well absorbed from the gastrointestinal tract. Penetrates the BBB. Metabolized in the liver. Excreted mainly by the kidneys (80%). T1 / 2 - 3-4 hours
Indications
Chronic myeloid leukemia - True polycythemia (erythremia) - Essential thrombocythemia - Osteomyelofibrosis - Melanoma - Malignant head and neck tumors, except for lip cancer (in combination with radiation therapy) - Cervical cancer (in combination with radiation therapy)
Contraindications
Hypersensitivity to hydroxycarbamide or any other excipient that is part of the drug. - Pregnancy and breastfeeding period. - Leukopenia below 2500 / mcl, thrombocytopenia below 100000 / mcl. - Children's age (safety and efficacy not established).
Precautionary measures
Care must be taken in patients with severely impaired renal function. It is not recommended to use hydroxycarbamide in patients with chicken pox (including recently postponed or after contact with the diseased), herpes zoster and other acute infectious diseases.
Use during pregnancy and lactation
Hydroxycarbamide is contraindicated during pregnancy. If necessary, use during lactation should stop breastfeeding. Women of childbearing age receiving hydroxycarbamide therapy should use reliable methods of contraception. Experimental studies have established the teratogenic and embryotoxic effects of hydroxycarbamide.
Dosage and administration
When choosing a regimen and doses in each individual case, you should be guided by the data of special literature. The drug is used inside. If swallowing is difficult, you can open the capsule, pour the contents into a glass of water and drink immediately. However, some water-insoluble auxiliary substances may remain on the surface of the solution.During treatment with the drug should take a sufficiently large amount of fluid. Resistant chronic myeloid leukemia. Continuous therapy. 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 an acceptable clinical response, treatment can continue indefinitely. Treatment should be suspended if the leukocyte count is less than 2500 / mm3 or the platelet count is less than 100,000 / mm3. After 3 days, the blood test is repeated. Treatment is resumed when the content of leukocytes and erythrocytes rises to an acceptable level (see above). Usually, the restoration of the content of leukocytes and erythrocytes occurs fairly quickly, otherwise, when combined use of the drug with radiation therapy, the latter can also be suspended. The development of anemia, even severe, does not require interruption of the course of treatment, provided adequate therapy (red blood cell transfusion). True polycythemia Treatment begins with a daily dose of 15–20 mg / kg. The dose is set individually, seeking to maintain the hematocrit at a level below 45%, and the number of platelets - below 400000 / mcl. In most patients, it is possible to achieve these indicators by constantly applying hydroxycarbamide in a daily dose of 500 to 1000 mg. Essential thrombocythemia. Usually, the drug Hydrea is prescribed in an initial daily dose of 15 mg / kg; then a dose is selected that maintains the number of platelets below 600000 / μl, without leading to a decrease in the number of white blood cells below 4000 / μl. Solid tumors, melanoma Intermittent therapy: - 80 mg / kg once a day every three days (6-7 doses). Continuous therapy: - 20-30 mg / kg daily once a day for 3 weeks. Head and neck carcinoma, cervical carcinoma 80 mg / kg once a day, every three days in combination with radiation therapy. Drug treatment begins no less than 7 days before the start of radiation therapy and continue during radiation therapy. After radiation therapy, the drug continues to be taken for an unlimited time with strict observation of the patient and in the absence of unusual or severe toxic reactions. Patients with impaired liver function. There are no indications for changing doses in this group of patients. Care should be taken to monitor blood counts in patients with impaired liver function. Patients with impaired renal function. Since hydroxyurea is excreted mainly through the kidneys, a dose reduction is necessary when prescribing the drug to such patients.For patients with renal insufficiency (creatinine clearance less than 60 ml / min), the drug is usually given at a dose of 15 mg / kg. Patients in the terminal stage of renal failure receive the drug at a dose of 15 mg / kg twice, with an interval of 7 days between doses: the first time after the 4-hour hemodialysis session, the second time before the hemodialysis session. Elderly patients As elderly patients are more likely to develop side effects when using Hydrea, than young patients, the recommended dose for patients in this group should not exceed 60 mg / kg per day.
Side effects
Infections: frequency unknown - gangrene; From the side of blood-forming organs: the frequency is unknown - suppression of the function of the bone marrow (leukopenia, anemia, thrombocytopenia). On the part of the digestive system: the frequency is unknown - hepatotoxicity, and pancreatitis, sometimes fatal (in HIV-infected patients who are simultaneously receiving antiretroviral therapy, in particular didanosine and stavudine); stomatitis, anorexia, nausea, vomiting, diarrhea, constipation, mucositis, dyspepsia, irritation of the gastric mucosa, ulceration of the mucous membrane of the gastrointestinal tract; increased activity of liver enzymes and plasma bilirubin concentration; On the part of the skin and skin appendages: the frequency is unknown - cutaneous vasculitis, maculo-papular rashes, facial erythema and peripheral erythema, skin ulceration, dermatomyositis-like skin changes, skin exfoliation, hyperpigmentation, erythema, atrophy of the skin and nails, peeling, purple-colored papules toxic skin vasculitis (including vasculitic ulceration and gangrene); rarely - alopecia, skin cancer. On the part of the nervous system: the frequency is unknown - dizziness, drowsiness, disorientation; headache, hallucinations, convulsions, peripheral neuropathy (in HIV-infected patients who are simultaneously receiving antiretroviral therapy, in particular, didanosine and stavudine), increased fatigue ,; On the part of the respiratory system: the frequency is unknown - pulmonary fibrosis, diffuse pulmonary infiltration, shortness of breath. On the part of the urinary system: the frequency is unknown - an increase in the content of uric acid in the blood serum, an increase in the content of urea nitrogen and creatinine in the blood plasma, urinary retention, interstitial nephritis, rarely - dysuria.Other: unknown frequency - chills, fever, general malaise, increased ESR, skin allergic reactions, asthenia, rarely - diffuse infiltration of the lungs, shortness of breath. who took hydroxycarbamide together with antiretroviral drugs, in particular didanosine in combination with stavudine or without it. Side effects observed with the simultaneous use of hydroxycarbamide and radiation therapy are the same as with monotherapy with the drug, mainly inhibition of bone marrow function (leukopenia, anemia) and irritation of the gastric mucosa. Taking hydroxycarbamide may increase certain side effects that are observed during radiation therapy, such as stomach discomfort and mucositis.
Overdose
Exceeding the recommended doses of Hydrea is manifested by changes in the mucous membranes and skin, soreness of the skin, violet erythema, swelling and peeling of the limbs, acute stomatitis and hyperpigmentation of the skin.
Interaction with other drugs
Perhaps increased mielodepressii in the case of prior therapy with cytotoxic drugs.
special instructions
Elderly patients may need to adjust the dosage regimen. When using hydroxycarbamide in patients with gout or nephrolithiasis, the risk of hyperuricemia increases. Combination with radiation therapy can lead to increased side effects that are associated with myelodepression and gastric mucosa. Erythema due to radiation may increase. Nausea, vomiting, anorexia caused by combined use with radiation therapy, as a result of the temporary cancellation of hydroxycarbamide may disappear. Before beginning and during treatment, a complete picture of the blood should be determined, including bone marrow and kidney and liver function. A blood test repeated at least 1 time / week. With a decrease in the number of leukocytes of less than 2500 / μl, and platelets less than 100 000 / μl, treatment should be stopped until the normal values of these indicators are restored. Possible changes in ESR (often increased). When anemia develops, it should be treated without interrupting the course of hydroxycarbamide,with the help of replacement erythrocyte mass transfusions. Changes in biochemical parameters are possible: an increase in the concentration of urea in the blood, creatinine, uric acid, an increase in the activity of hepatic transaminases. It is not recommended to vaccinate patients and their families.