Hydroxycarbamide medak
Hydroxycarbamide medak: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Hydroxycarbamide medac
ATX code: L01XX05
Active ingredient: hydroxycarbamide (Hydroxycarbamide)
Producer: Medak, GmbH (Medac, GmbH) (Germany)
Description and photo update: 2019-11-07
Prices in pharmacies: from 1159 rubles.
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Hydroxycarbamide medak - antimetabolite, antineoplastic agent.
Release form and composition
Dosage form - capsules: size No. 0, hard gelatinous, with an opaque white body and lid; content - almost white powder (10 pcs. in a blister, in a cardboard box 5 or 10 blisters together with instructions for use of Hydroxycarbamide medak).
Composition of 1 capsule:
- active ingredient: hydroxycarbamide - 500 mg;
- excipients: disodium citrate, calcium citrate, magnesium stearate, lactose monohydrate;
- capsule shell: gelatin, titanium dioxide (E 171).
Pharmacological properties
Pharmacodynamics
The active ingredient of Hydroxycarbamide medak is hydroxycarbamide, a phase-specific cytostatic agent (antimetabolite, according to some reports, with an alkylating property), which acts in the S phase of the cell cycle.
Hydroxycarbamide medak blocks cell growth in the G1 ‒ S interphase. This is of great importance for simultaneous radiation therapy, since the drug promotes the appearance of synergistic sensitivity of tumor cells in the G1 phase to radiation.
The drug enhances the effect of ribonucleoside diphosphate reductase (an inhibitor of RNA reductase), which inhibits DNA synthesis. Hydroxycarbamide has no effect on RNA and protein synthesis.
Pharmacokinetics
Absorption of hydroxycarbamide from the gastrointestinal tract (GIT) after oral administration occurs quickly. Within 2 hours, C max (maximum plasma concentration) is reached. There is no information on the effect of food when taken simultaneously with the drug.
Hydroxycarbamide is rapidly distributed throughout the tissues of the body, penetrates the BBB (blood-brain barrier). The concentration in the cerebrospinal fluid is 10–20% of the plasma concentration, in the ascitic fluid - from 15 to 50%. The drug accumulates in erythrocytes and leukocytes.
Undergoes partial metabolism in the kidneys and liver. The half-life is 3-4 hours. About 80% of the dose received is excreted in the urine within 12 hours after administration, of which about 50% is unchanged hydroxycarbamide, small amounts are excreted in the form of urea. Also, the drug is removed from the body through the respiratory tract in the form of carbon dioxide. Already 24 hours after taking Hydroxycarbamide medak is not detected in plasma.
Indications for use
- melanoma;
- chronic myeloid leukemia;
- osteomyelofibrosis;
- essential thrombocythemia;
- polycythemia vera (erythremia);
- cervical cancer (in combination with radiation therapy);
- malignant tumors of the neck and head, with the exception of lip cancer (in conjunction with radiation therapy).
Contraindications
Absolute:
- thrombocytopenia <100 x 10 9 / l, leukopenia <2.5 x 10 9 / l;
- pregnancy and breastfeeding;
- age up to 18 years;
- hypersensitivity to any component of the drug.
Hydroxycarbamide medak is used with caution in the following cases:
- lactase deficiency, glucose-galactose malabsorption, lactose intolerance;
- anemia (must be corrected before starting treatment);
- renal and / or hepatic impairment;
- previous chemotherapy or radiotherapy.
Hydroxycarbamide medak, instructions for use: method and dosage
Hydroxycarbamide medak should be taken orally: swallow the capsules whole and drink plenty of water (1 glass). Patients who have difficulty swallowing whole capsules are allowed to open them and dissolve the powder in a glass of water (some water-insoluble auxiliary components of the capsule can float on the surface of the solution - this is the norm). During the period of therapy, it is recommended to consume plenty of fluids.
Treatment is carried out under the close supervision and guidance of a physician with relevant experience. The optimal dosages are set individually, taking into account the real or ideal weight of the patient (choose a lower value).
Standard dosage regimens of Hydroxycarbamide medac:
- melanoma, solid tumors: continuous therapy - 20-30 mg / kg per day for 3 weeks, intermittent therapy - 80 mg / kg every 3 days (6-7 doses);
- essential thrombocythemia: the initial daily dose is 15 mg / kg, then the dose is selected in such a way that the number of platelets is maintained at a level of at least 600 x 10 9 / l, and there is no decrease in the number of leukocytes below 4 x 10 9 / l;
- osteomyelofibrosis: the initial daily dose is 5–20 mg / kg, the maintenance dose is 10 mg / kg;
- carcinoma of the neck / head / cervix: 80 mg / kg 1 time per day every third day against the background of radiation therapy. Reception of Hydroxycarbamide medak begins at least 7 days before the start of radiation therapy. After the end of radiation therapy, the drug can be used indefinitely (careful monitoring is required for the development of severe or unusual toxicity reactions);
- polycythemia vera: initial daily dose is 15–20 mg / kg. They try to select a further dose in such a way that it maintains the hematocrit at a level of <45%, and the number of platelets - <400 x 10 9 / L (in most cases, such indicators can be achieved with a daily dose of hydroxycarbamide of 500-1000 mg). In cases where the level of hematocrit and the number of platelets are successfully controlled by the applied dose of Hydroxycarbamide medac, treatment is continued indefinitely;
- resistant chronic myeloid leukemia: at the beginning of therapy - 40 mg / kg per day. The dose is adjusted depending on the content of leukocytes in the blood plasma. If their number is <20 x 10 9 / l, then the dose is halved. With the development of leukopenia, the dose is selected in such a way that it ensures the maintenance of leukocytes at the level of 5‒10 x 10 9 / L. With a decrease in the number of leukocytes below 5 x 10 9 / l, the dose of the drug is also reduced, it can be increased only when the number of leukocytes reaches at least 10 x 10 9 / l. If the number of leukocytes is <2.5 x 10 9 / l or platelets <100 x 10 9 / l, drug treatment is stopped, and continues only after the number of leukocytes and platelets is restored.
The evaluation period for the antitumor efficacy of Hydroxycarbamide Medak is 6 weeks. Treatment is stopped in case of significant deterioration in the course of the disease. After a clinically significant improvement in the condition, therapy is continued indefinitely.
Patients with impaired renal function require dose reduction. Recommended daily doses for this category of patients, depending on creatinine clearance (CC):
- CC 30-60 ml / min: 15 mg / kg;
- CC <15 ml / min (end-stage renal failure): a dose of 15 mg / kg is prescribed twice: the first dose - after the end of 4-hour hemodialysis, the second dose - before the dialysis session after 7 days.
Elderly patients, due to the increased likelihood of undesirable effects, are not recommended to exceed a daily dose of 60 mg / kg.
Side effects
The frequency of the side effects described below is graded as follows: ≥ 1/10 - very common, from ≥ 1/100 to <1/10 - often, from ≥ 1/1000 to <1/100 - infrequently, from ≥ 1 / 10,000 to <1/1000 - rarely, <1/10,000 - very rare (including single messages), unknown frequency - taking into account the available data, it is not possible to accurately estimate the frequency of development:
- disorders of the nervous system: rarely - disorientation, increased fatigue, dizziness, drowsiness, headache, hallucinations, convulsions; unknown frequency - peripheral neuropathy [in patients with HIV (human immunodeficiency virus), receiving concurrent antiretroviral therapy, in particular stavudine and didanosine];
- infections: unknown frequency - gangrene;
- reactions from the digestive system: often - constipation / diarrhea; infrequently - nausea, anorexia, stomatitis, ulceration of the gastrointestinal tract mucosa, vomiting, increased plasma bilirubin concentration and liver enzyme activity; unknown frequency - hepatotoxicity and pancreatitis up to death (in HIV-infected patients receiving concomitant antiretroviral therapy);
- phenomena from the urinary system: infrequently - transient dysfunction of the renal tubules, accompanied by an increase in creatinine, urea and the concentration of uric acid in the blood plasma; rarely - dysuria; very rarely - interstitial nephritis, renal failure;
- respiratory system disorders: rarely - allergic alveolitis, acute reactions (shortness of breath, fever, diffuse infiltrates in the lungs); unknown frequency - pulmonary fibrosis;
- effects of the immune system: rarely - hypersensitivity or intolerance reactions;
- phenomena on the part of the hematopoietic organs: often - megaloblastosis, bone marrow suppression, leukopenia; infrequently - thrombocytopenia, anemia;
- reactions from the subcutaneous tissues and skin: infrequently - macular-papular rash, palmar-plantar syndrome, facial erythema; rarely - alopecia; very rarely - peeling of the skin, radiation keratosis, purple papules, pruritus, skin ulcers (especially in the lower leg), atrophy or hyperpigmentation of the skin and nails, skin changes similar to dermatomyositis, skin cancer (squamous cell, basal cell carcinoma); unknown frequency - peripheral erythema, cutaneous vasculitis, including toxic in patients with myeloproliferative diseases (including vasculitic ulceration, gangrene);
- others: infrequently - general weakness, malaise, drug fever, chills; rarely - impaired fertility (azoospermia, amenorrhea), tumor decay syndrome; very rarely - an increase in the erythrocyte sedimentation rate; unknown frequency - hyponatremia, hyperkalemia.
Overdose
When taking Hydroxycarbamide medak in doses that exceed the recommended several times, it is possible to develop severe reactions from the mucous membranes and skin: stomatitis, edema of the palms and feet, purple erythema, pain, intense hyperpigmentation of the skin, hyperkeratosis of the hands and feet.
After taking an excessive dose of Hydroxycarbamide, medac should be given gastric lavage. Treatment is symptomatic under the control of indicators of the hematopoietic system. If necessary, hemodialysis is performed.
special instructions
Hydroxycarbamide medak is prescribed only by a doctor with appropriate experience in anticancer treatment. Before each course and periodically during therapy, monitoring of the function of the bone marrow, liver, and kidneys is required. At least once a week during the entire course, it is necessary to carry out a clinical blood test, including the determination of the number of platelets, the level of hemoglobin and the expanded leukocyte formula. If a decrease in the number of platelets below 100 x 10 9 / l or leukocytes is less than 2.5 x 10 9 / l is detected, the use of hydroxycarbamide medak is suspended until hematological parameters are normalized.
Patients opening capsules (if there are problems with swallowing whole capsules), special care should be taken to avoid inhalation of the powder contained in them and its contact with mucous membranes and skin.
During therapy, it is recommended to monitor the condition of the skin, since individual cases of the development of squamous cell carcinoma of the skin have been reported.
In the early stages of treatment, the occurrence of moderate megaloblastic erythropoiesis is often noted. Morphological changes resemble pernicious anemia, but they are not caused by lack of folic acid or vitamin B 12.
In patients with existing anemia, Hydroxycarbamide Medak can be used only after correcting the condition.
Against the background of anticancer therapy, the development of myelosuppression, mainly leukopenia, is possible. Rarely, anemia and thrombocytopenia occur, even less often - without prior leukopenia. Anemia (even severe) is stopped without stopping treatment with hydroxycarbamide. Patients who have recently undergone chemotherapy with other drugs or intensive radiation therapy are at greatest risk of developing myelosuppression. In the latter case, Hydroxycarbamide medak is used with extreme caution, due to the danger of exacerbation of post-radiation erythema and increased severity of side reactions (dyspepsia, ulcerative lesions of the gastrointestinal tract, bone marrow aplasia).
Hydroxycarbamide medak is able to reduce the clearance of iron from blood plasma and reduce the efficiency of iron utilization by erythrocytes, but does not affect the life span of the latter.
Cases of pancreatitis and hepatotoxicity (with a possible fatal outcome) have been reported in HIV-infected patients receiving antiretroviral drugs at the same time. In this regard, during treatment, it is required to intensively monitor the activity of transaminases in the blood plasma, as well as the concentration of creatinine and uric acid.
Occasionally, Hydroxycarbamide Medak causes painful ulceration of the skin on the legs. They are difficult to treat, and therefore require the abolition of anticancer therapy - in this case, ulcers usually heal within 2 weeks.
With prolonged use of hydroxycarbamide in patients with myeloproliferative diseases (thrombocythemia, polycythemia vera), secondary leukemia may develop.
In patients receiving hydroxycarbamide, false-positive test results for lactic acid, urea and uric acid may be obtained, since the drug interacts with enzymes such as lactate dehydrogenase, urease and uricase.
Women and men of reproductive age should use effective contraceptive methods before starting the use of Hydroxycarbamide medac, during therapy and for 3 months after its end. Hydroxycarbamide has genotoxic activity, therefore, when planning a pregnancy after the end of the course of treatment, it is recommended to consult a geneticist.
Influence on the ability to drive vehicles and complex mechanisms
When using Hydroxycarbamide, medak is recommended to refrain from performing any potentially dangerous work (including driving a car), since the drug often causes side effects such as blurred consciousness, disorientation (disorientation in space), and dizziness.
Application during pregnancy and lactation
Hydroxycarbamide medak is contraindicated during pregnancy because it crosses the placental barrier. If pregnancy occurs during the period of anticancer therapy, consultation with a geneticist is required.
Hydroxycarbamide medak is excreted in mother's milk. Breastfeeding should be discontinued if drug treatment is necessary during lactation.
Pediatric use
Up to 18 years of age, capsules of Hydroxycarbamide Medak 500 mg are not prescribed due to the lack of sufficient experience in its use in this age group of patients.
With impaired renal function
The drug is excreted mainly by the kidneys, therefore, if the function of this organ is impaired, a decrease in the dose of Hydroxycarbamide medak is required. With a creatinine clearance of 30-60 ml / min, the recommended dose is 15 mg / kg. For patients with end-stage renal failure, a dose of 15 mg / kg is prescribed twice: the first dose - after the end of 4-hour hemodialysis, the second dose - before the dialysis session after 7 days.
For violations of liver function
There is no data on the need to adjust the dose of Hydroxycarbamide medac for patients with impaired hepatic function. During treatment, it is necessary to carefully monitor blood counts.
Use in the elderly
In elderly patients, the likelihood of unwanted effects increases, so it is not recommended to exceed a daily dose of 60 mg / kg.
Drug interactions
When using Hydroxycarbamide medak against the background of radiation therapy or in conjunction with other myelosuppressive drugs, it is possible to increase the degree of suppression of bone marrow function and increase the risk of developing other adverse reactions.
Hydroxycarbamide can increase the level of uric acid in the blood. With the combined use of drugs that enhance the excretion of uric acid, the risk of developing urate nephropathy increases. When using such a combination, dose adjustment of drugs or additional prescription of allopurinol is required.
The drug enhances the antiretroviral effect of nucleoside reverse transcriptase inhibitors (NRTIs) such as stavudine and didanosine. Hydroxycarbamide medak inhibits DNA synthesis and HIV replication by decreasing the intracellular deoxynucleotide. Also, the drug is able to enhance the side effects of drugs in this group (peripheral neuropathy, pancreatitis, hepatotoxicity).
Analogs
Analogues of Hydroxycarbamide medak are: 5-Fluorouracil-Ebeve, Aleksan, Alimta, Atrians, Vaidaza, Vero-Methotrexate, Gemzar, Gemtaz, Gemcitover, Dacogen, Ispolat, Cabetsin, Xeloda, Leikladin, Mitoxgemultanel, Ongeftzin, Ungeftin, Cytogem, Cytosar, Evoltra, etc.
Terms and conditions of storage
Store at a temperature not exceeding + 25 ° С in a dark place. Keep out of the reach of children.
Shelf life is 4 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Hydroxycarbamide Medak
Considering the specificity of the use of the drug, reviews of Hydroxycarbamide medak are few. Patients indicate that the drug can slow down the rate of growth and progression of the malignant neoplasm. The heavy tolerance of anticancer therapy is noted, especially at the beginning of treatment. The most frequently mentioned is a sharp decline in strength, which is probably due to a decrease in the level of hemoglobin in the blood.
Price for Hydroxycarbamide medak in pharmacies
Depending on the region of sale and the pharmacy network, the price for Hydroxycarbamide Medak 500 mg is approximately from 979 to 1243 rubles. per pack of 100 capsules.
Hydroxycarbamide medak: prices in online pharmacies
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Drug name Price Pharmacy |
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Hydroxycarbamide medak 500 mg capsules 100 pcs. 1159 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
