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Title: Hydroxycarbamide  
Author: World Heritage Encyclopedia
Language: English
Subject: List of drugs: Hf-Hz, WHO Model List of Essential Medicines, Hydrea, Urea, Potassium cyanate
Collection: Antineoplastic Antimetabolites, Iarc Group 3 Carcinogens, Ureas
Publisher: World Heritage Encyclopedia


Structural formula
Systematic (IUPAC) name
Clinical data
Trade names Apo-Hydroxyurea, Droxia, Hydrea
Licence data EMA:, US FDA:
  • AU: D
  • US: D (Evidence of risk)
Legal status
Routes of
Pharmacokinetic data
Metabolism Hepatic (to CO2 and urea)
Biological half-life 2-4 hours
Excretion Renal and lungs
CAS Registry Number  Y
ATC code L01
PubChem CID:
DrugBank  Y
ChemSpider  Y
Chemical data
Formula CH4N2O2
Molecular mass 76.0547 g/mol

Hydroxycarbamide (health system.[1]


  • Medical uses 1
  • Side effects 2
  • Mechanism of action 3
  • Synthesis 4
  • Natural occurrence 5
  • References 6

Medical uses

Hydroxycarbamide is used for the following indications:

Side effects

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.[10]

Due to its 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.[11] Moreover, because of this, severe anemia and neutropenia are contradicted.

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.[12]

Mechanism of action

Hydroxycarbamide decreases the production of deoxyribonucleotides[13] via inhibition of the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals as they are involved in the reduction NDPs.[12]

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 chain synthesis necessary for fetal hemoglobin production (which inhibits the formation of sickle hemoglobin aggregates). A few red cell clones called F cells are progeny of a small pool of immature committed erythroid precursors (BFU-e) that retain the ability to produce HbF.[12][14]


Hydroxyurea was first synthesized in 1869 by Dresler and Stein from hydroxylamine and hydrogen cyanate; the industrial process is analogous.[15] Hydroxyurea may also be synthesized by reaction of ethyl carbamate with hydroxylamine; hydroxylamine displaces the ester to give the amide.[16]

Hydroxyurea is made by reacting sodium cyanate with hydroxylamine. In this reaction, hydroxylamine hydrochloride and a basic ion-exchange resin are used.

  • A. Hantzsch, Justus Liebigs Annalen der Chemie, 299, 99 (1898).
  • J.P. Graham, U.S. Patent 2,705,727 (1955).

Hydroxyrurea acts by suppressing dihydrophosphate reductase, an enzyme that reduces ribonucleotides into deoxyribonucleotides necessary for DNA synthesis. This drug causes a sharp decrease in the amount of white blood cells in severe leukemias. It is used for leukemias, melanomas, and carcinomas.

Synonyms of this drug are litalir, hydrea, onco-carbide, and others.

Natural occurrence

Hydroxyurea has been reported as endogenous in human blood plasma at concentrations of approximately 30 to 200 ng/mL.[17]


  1. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  2. ^ Harrison CN, Campbell PJ, Buck G, et al. (July 2005). "Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia". N. Engl. J. Med. 353 (1): 33–45.  
  3. ^ Lanzkron S, Strouse JJ, Wilson R, et al. (June 2008). "Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease". Ann. Intern. Med. 148 (12): 939–55.  
  4. ^ Frank I, Bosch RJ, Fiscus S, et al. (September 2004). "Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307". AIDS Res. Hum. Retroviruses 20 (9): 916–26.  
  5. ^ Sharma VK, Dutta B, Ramam M (2004). "Hydroxyurea as an alternative therapy for psoriasis". Indian J Dermatol Venereol Leprol 70 (1): 13–7.  
  6. ^ Rustin, MH (November 2012). "Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data". Br J Dermatol 167 (Suppl 3): 3–11.  
  7. ^ Escribano, L.; Álvarez-Twose, I. N.; Sánchez-Muñoz, L.; Garcia-Montero, A.; Núñez, R.; Almeida, J.; Jara-Acevedo, M.; Teodósio, C.; et al. (2009). "Prognosis in adult indolent systemic mastocytosis: A long-term study of the Spanish Network on Mastocytosis in a series of 145 patients". Journal of Allergy and Clinical Immunology 124 (3): 514–521.  
  8. ^ Dalziel, K.; Round, A.; Stein, K.; Garside, R.; Price, A. (2004). "Effectiveness and cost-effectiveness of imatinib for first-line treatment of chronic myeloid leukaemia in chronic phase: A systematic review and economic analysis". Health technology assessment (Winchester, England) 8 (28): iii, ii1–120.  
  9. ^ Koç A, Wheeler LJ, Mathews CK, Merrill GF (January 2004). "Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools". J. Biol. Chem. 279 (1): 223–30.  
  10. ^ Liebelt, E.; Balk, S.; Faber, W.; Fisher, J.; Hughes, C.; Lanzkron, S.; Lewis, K.; Marchetti, F.; Mehendale, H.; Rogers, J. M.; Shad, A. T.; Skalko, R. G.; Stanek, E. J. (2007). "NTP-CERHR expert panel report on the reproductive and developmental toxicity of hydroxyurea". Birth defects research. Part B, Developmental and reproductive toxicology 80 (4): 259–366.  
  11. ^ Longe, Jacqueline L. (2002). Gale Encyclopedia Of Cancer: A Guide To Cancer And Its Treatments. Detroit: Thomson Gale. pp. 514–516.  
  12. ^ a b c Platt OS (2008). "Hydroxyurea for the treatment of sickle cell anemia". N. Engl. J. Med. 358 (13): 1362–9.  
  13. ^ "hydroxyurea" at Dorland's Medical Dictionary
  14. ^ Cokic VP, Smith RD, Beleslin-Cokic BB, et al. (2003). "Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase". J Clin Invest 111 (2): 231–9.  
  15. ^ Lunghi, A; Aloni, C; Gigante, L; Mazzei, N; Cardillo, P (2002). "Hydroxyurea explosion: a thermoanalytical and calorimetric study". Journal of Loss Prevention in the Process Industries 15 (6): 489–495.  
  16. ^ R. Deghenghi (1973). "Hydroxyurea".  
  17. ^ Kettani, T; Gulbis, B; Ferster, A; Kumps, A (2009). "Plasma hydroxyurea determined by gas chromatography-mass spectrometry". Journal of Chromatography B 877 (4): 446–450.  
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