|Trade names||Droxia, Hydrea, others|
|AHFS/Drugs.com||International Drug Names|
|Metabolism||liver (to CO2 and urea)|
|Biological half-life||2-4 hours|
|Excretion||Renal and lungs|
|Chemical and physical data|
|Molar mass||76.0547 g/mol|
|3D model (Jmol)|
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, chronic myelogenous leukemia, cervical cancer, and polycythemia vera. In sickle-cell disease it decreases the number of attacks. It is taken by mouth.
Common side effects include bone marrow suppression, fevers, loss of appetite, psychiatric problems, shortness of breath, and headaches. There is also concerns that it increases the risk of later cancers. Use during pregnancy is typically harmful to the baby. Hydroxycarbamide is in the antineoplastic family of medications. It is believed to work by blocking the making of DNA.
Hydroxycarbamide was approved for medical use in the United States in 1967. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Hydroxycarbamide is available as a generic medication. The wholesale cost in the developing world is about 0.35 to 0.47 USD per day. In the United States it costs less than 25 USD a month.
Hydroxycarbamide is used for the following indications:
- Myeloproliferative disease (primarily polycythemia vera and essential thrombocytosis). It has been found to be superior to anagrelide for the control of ET.
- Sickle-cell disease (increases production of fetal hemoglobin that then reduces the tendency of sickle cells to sickle, as well as reducing white blood cells that contribute to the general inflammatory state in sickle cell patients.
- Second line treatment for psoriasis (slows down the rapid division of skin cells)
- Systemic mastocytosis
- Chronic myelogenous leukemia (largely replaced by imatinib, but still in use for its cost-effectiveness)
Reported side-effects are: drowsiness, nausea, vomiting and diarrhea, constipation, mucositis, anorexia, stomatitis, bone marrow toxicity (dose-limiting toxicity; may take 7–21 days to recover after the drug has been discontinued), alopecia (hair loss), skin changes, abnormal liver enzymes, creatinine and blood urea nitrogen.
Due to its negative effect on the bone marrow, regular monitoring of the full blood count is vital, as well as early response to possible infections. In addition, renal function, uric acid and electrolytes, as well as liver enzymes, are commonly checked. Moreover, because of this, severe anemia and neutropenia are contraindicated.
Hydroxycarbamide has been used primarily for the treatment of myeloproliferative diseases, which has an inherent risk of transforming to acute myeloid leukemia. There has been a longstanding concern that hydroxycarbamide itself carries a leukemia risk, but large studies have shown that the risk is either absent or very small. Nevertheless, it has been a barrier for its wider use in patients with sickle-cell disease.
Mechanism of action
Hydroxycarbamide decreases the production of deoxyribonucleotides via inhibition of the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals as they are involved in the reduction of nucleoside diphosphates (NDPs).
In the treatment of sickle-cell disease, hydroxycarbamide increases the concentration of fetal hemoglobin. The precise mechanism of action is not yet clear, but it appears that hydroxycarbamide increases nitric oxide levels, causing soluble guanylyl cyclase activation with a resultant rise in cyclic GMP, and the activation of gamma globin gene expression and subsequent gamma chain synthesis necessary for fetal hemoglobin (HbF) production (which does not polymerize and deform red blood cells like the mutated HbS, responsible for sickle cell disease). Adult red cells containing more than 1% HbF are termed F cells. These cells are progeny of a small pool of immature committed erythroid precursors (BFU-e) that retain the ability to produce HbF. Hydroxyurea also suppresses the production of granulocytes in the bone marrow which has a mild immunosppressive effect particularly at vascular sites where sickle cells have occluded blood flow. 
Brand names include: Hydrea, Litalir, Droxia, and Siklos
Hydroxyurea has been reported as endogenous in human blood plasma at concentrations of approximately 30 to 200 ng/mL.
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