Also Known As: Hydroxyurea, Hydroxycarbamide, Hydrea, Droxia
Hydroxycarbamide (INN) or hydroxyurea (brand names include Hydrea and Droxia) is an antineoplastic drug, first synthesized in 1869, used in myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia. It is also used to reduce the rate of painful attacks in sickle-cell disease and has antiretroviral properties in diseases such as AIDS.
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 (breaks down cells that are prone to sickle, as well as increasing fetal hemoglobin content)
- AIDS as an adjunct to ddI in combination antiretroviral therapies
- 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)
- Biochemical research as a DNA replication inhibitor that causes deoxyribonucleotide depletion and results in DNA double strand breaks near replication forks (see DNA repair)
One mechanism of action is thought to be based on its reduction of production of deoxyribonucleotides via inhibition of the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals as they are involved in the reduction 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 gammaglobin synthesis necessary for fetal hemoglobin (by removing the rapidly dividing cells that preferentially produce sickle hemoglobin).