Hydroxycarbamide
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Clinical Pharmacology
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. Gets through the BBB. Metabolized in the liver. Excreted mainly by the kidneys (80%). T1/2 - 3-4 hours
Indications
- Chronic myeloid leukemia;
- melanoma;
- ovarian cancer;
- cervical cancer;
- uterine choriocarcinoma;
- head and neck tumors;
- brain tumor;
- erythremia.
Composition
1 capsule contains:
Active substances: hydroxycarbamide 500 mg.
Hydroxycarbamide is marketed under different brands and generic names, and comes in different dosage forms:
Brand name | Manufacturer | Country | Dosage form |
---|---|---|---|
Hydrea | Bristol-Myers Squibb | USA | capsules |
Hydroxycarbamide Medak | Medak GmbH | Germany | capsules |
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Dosage and Administration
Dosage regimen should be deterimined individually, depending on the evidence and the stage of the disease, the state of the hematopoietic system, the scheme of antitumor therapy.
Adverse reactions
From the hemopoietic system: leukopenia, thrombocytopenia, anemia.
From the digestive system: stomatitis, anorexia, nausea, vomiting, diarrhea, constipation; rarely - liver dysfunction.
From the side of the central nervous system: feeling tired, headache, drowsiness, dizziness, hallucinations, convulsions.
On the part of the respiratory system: in some cases - diffuse pulmonary infiltrates, accompanied by fever and shortness of breath.
From the urinary system: difficulty urinating; rarely - impaired renal function.
Dermatological reactions: alopecia, maculo-papular rash, erythema.
Other: fever, chills.
Contraindications
- Leukopenia less than 2500 / mcl;
- thrombocytopenia less than 100,000 / μl;
- severe anemia;
- pregnancy;
- hypersensitivity to hydroxycarbamide.
Drug interactions
May increase mielodepressii in the case of prior therapy with cytotoxic drugs.
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.
In experimental studies The teratogenic and embryotoxic effects of hydroxycarbamide have been established.
Special instructions
Care must be taken in patients with severe renal impairment.
Do not recommend the use of hydroxycarbamide in patients with chickenpox (including recently transferred or after contact with the sick), herpes zoster and other acute infectious diseases.
Elderly patients may require a dosage regimen adjustment.
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 damage to the 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 and during treatment, a complete blood picture should be determined, including bone marrow examination, as well as 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 normal values of these indicators are restored. Possible changes in ESR (often increased).
With the development of anemia, it should be treated without interrupting the course of hydroxycarbamide, using replacement transfusions of erythrocyte mass.
Changes in biochemical parameters are possible: an increase in the blood concentration of urea, creatinine, uric acid, an increase in the activity of hepatic transaminases.
Do not recommend vaccinating patients and their families.
Overdosage
Symptomatic treatment, because no specific antidote; not subject to dialysis.
- Brand name: Hydrea
- Active ingredient: Hydroxycarbamide
- Dosage form: Capsules
- Manufacturer: Bristol-Myers Squibb
- Country of Origin: USA
Studies and clinical trials of Hydroxycarbamide (Click to expand)
- Acute tumor lysis syndrome secondary to hydroxycarbamide in chronic myelomonocytic leukemia
- Hydroxycarbamide-induced dermopathy
- Hydroxycarbamide: a treatment for lichen sclerosus?
- Treatment with hydroxycarbamide for intermedia thalassaemia: decrease of efficacy in some patients during long-term follow up
- Gene expression profiles of erythroid precursors characterise several mechanisms of the action of hydroxycarbamide in sickle cell anaemia
- Hydroxycarbamide in combination with azacitidine or decitabine is antagonistic on DNA methylation inhibition
- Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia
- Induction of gamma-globin gene transcription by hydroxycarbamide in primary erythroid cell cultures from Lepore patients
- Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia
- The presence of α-thalassaemia trait blunts the response to hydroxycarbamide in patients with sickle cell disease
- Hydroxycarbamide and erythropoietin in the preoperative management of children with sickle cell anaemia undergoing moderate risk surgery
- A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process
- Desensitization to hydroxycarbamide following long-term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients
- Clinical evaluation of the European LeukaemiaNet criteria for clinicohaematological response and resistance/intolerance to hydroxycarbamide in essential thrombocythaemia
- Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients
- The effects of hydroxycarbamide and magnesium on haemoglobin SC disease: results of the multi-centre CHAMPS trial
- Chromosome damage and repair in children with sickle cell anaemia and long-term hydroxycarbamide exposure
- Hydroxycarbamide-induced pneumonitis
- Nail pigmentation due to hydroxycarbamide
- Methaemoglobinaemia caused by hydroxycarbamide (hydroxyurea) ingestion in a dog
- Hydroxycarbamide (hydroxyurea) toxicity in dogs
- Comparison between anagrelide and hydroxycarbamide in their activities against haematopoietic progenitor cell growth and differentiation: selectivity of anagrelide for the megakaryocytic lineage
- Prognostic implications of leg ulcers from hydroxycarbamide therapy in patients with essential thrombocythaemia
- Effects of co-existing α-thalassaemia in sickle cell disease on hydroxycarbamide therapy and circulating nucleic acids