Hydroxyurea

Aka: Hydroxyurea, Droxia, Hydrea, Hydroxycarbamide

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II. Mechanism: Sickle Cell Anemia

  1. Increases production of fetal Hemoglobin (HbF) which does not sickle

III. Indications

  1. Malignancy
    1. Polycythemia Vera
      1. First-line agent indicated in high risk disease (history of thrombosis or age over 60 years old)
    2. Chronic myelocytic Leukemia
    3. Head and Neck Squamous Cell Cancer
    4. Melanoma
  2. Sickle Cell Anemia
    1. Indications in adults
      1. Sickle Cell Crisis 3 or more times in 12 months
      2. Severe or recurrent Acute Chest Syndrome
      3. Severe symptomatic chronic Anemia affecting functional status
      4. Sickle cell associated pain significantly impacting function or quality of life
    2. Indications in children over age 9 months
      1. All children over age 9 months should be offered Hydroxyurea to reduce complications

IV. Adverse Effects

  1. Anemia
  2. Neutropenia
  3. Oral Ulcers
  4. Skin Ulcers
  5. Hyperpigmentation
  6. Leukemogenicity risk in Polycythemia Vera (Exercise caution in age under 40 years old)
    1. Leukemic transformation 0.4% persons per year
    2. Myelofibrosis 5% at five years, 33.7% at 10 years
    3. Ferrari (2019) Hematologica 104(12): 2391-9 [PubMed]

V. Contraindications

  1. Pregnancy
  2. Lactation

VI. Monitoring: Sickle Cell Anemia

  1. Baseline
    1. Complete Blood Count with differential
    2. Reticulocyte Count
    3. Hemoglobin F quantitative measurement
    4. Comprehensive metabolic panel (Renal Function tests, Liver Function Tests)
    5. Pregnancy Test
  2. Labs while adjusting dose (every 4 weeks or more)
    1. Reticulocyte Count
    2. Complete Blood Count with differential and Platelets
      1. Maintain Absolute Neutrophil Count (ANC) > 2,000/mm3
      2. Maintain Platelet Count >80,000/mm3
  3. Labs when cytopenia occurs (every 1 week)
    1. Reticulocyte Count
    2. Complete Blood Count with differential and Platelets
  4. Periodic labs when on stable dose (every 2-3 months)
    1. Reticulocyte Count
    2. Complete Blood Count with differential and Platelets
    3. Hemoglobin F quantitative measurement may be obtained to evaluate for response

VII. Management: Sickle Cell Anemia

  1. Often managed in conjunction with Sickle Cell Disease specialist
  2. Trial for minimum of 6 months before assessing efficacy
  3. Encourage compliance for maximal effect
  4. Starting Doses
    1. Obtain baseline labs as above prior to initiating Hydroxyurea
    2. Arrange reliable Contraception for while on Hydroxyurea
    3. Dosing: Infants and Children
      1. Hydroxyurea 20 mg/kg daily
    4. Dosing: Adults with normal Renal Function
      1. Hydroxyurea 15 mg/kg (round up to nearest 500 mg) daily
    5. Dosing: Adults with Chronic Kidney Disease
      1. Hydroxyurea 5-10 mg/kg daily
  5. Adjusting dose
    1. See lab monitoring as above
    2. Maximum daily dose: 35 mg/kg/day
    3. Decreasing dose
      1. Indications
        1. Neutropenia (ANC <2000/mm3)
        2. Thrombocytopenia (Platelet Count <80,000/mm3)
      2. Approach
        1. Consult with specialist
        2. In some infants and children, ANC >1250/mm3 (instead of 2000/mm3) may be acceptable
        3. Increase lab monitoring to weekly as above
        4. Reduce Hydroxyurea dose by 5 mg/kg/day
    4. Increasing dose
      1. Target ANC 2000 to 4000/mm3
      2. Increase by 5 mg/kg/day increments every 8 weeks

VIII. Efficacy: Sickle Cell Anemia

  1. Full benefits may not be seen for the first 6 months after starting Hydroxyurea
  2. Reduces Sickle Cell Anemia mortality and hospitalizations (fewer episodes of crisis and Acute Chest Syndrome)
  3. Reduces Sickle Cell Crisis by 50%
  4. Steinberg (2003) JAMA 289:1645-51 [PubMed]

IX. Resources

  1. NIH: NHLBI Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014
    1. https://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines

X. References

  1. Yawn (2015) Am Fam Physician 92(12): 1069-76 [PubMed]

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Related Studies

Cost: Medications

hydroxyurea (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
HYDROXYUREA 500 MG CAPSULE Generic $0.32 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

Ontology: hydroxyurea (C0020402)

Definition (NCI_NCI-GLOSS) An anticancer drug that belongs to the family of drugs called antimetabolites.
Definition (NCI) A monohydroxyl-substituted urea (hydroxycarbamate) antimetabolite. Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby preventing cells from leaving the G1/S phase of the cell cycle. This agent also exhibits radiosensitizing activity by maintaining cells in the radiation-sensitive G1 phase and interfering with DNA repair. (NCI04)
Definition (MSH) An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
Definition (CSP) ribonucleotide reductase inhibitor which thereby lowers intracellular dNTP pools and slows DNA replication and repair; used as antineoplastic, cell devision inhibitor, and possible chemotherapy for sickle cell anemia.
Definition (PDQ) A monohydroxyl-substituted urea (hydroxycarbamate) antimetabolite. Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby preventing cells from leaving the G1/S phase of the cell cycle. This agent also exhibits radiosensitizing activity by maintaining cells in the radiation-sensitive G1 phase and interfering with DNA repair. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40685&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40685&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C560" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D006918
SnomedCT 387314007, 56602009
English Hydroxycarbamid, Hydroxyurea, Urea, hydroxy-, hydroxyurea (medication), Hydroxycarbamide, HYDROXYUREA, Hydroxyurea [Chemical/Ingredient], hydroxy urea, hyd, hydroxycarbamide, Hydroxyurea (product), Hydroxyurea (substance), HYD, HU, hydroxyurea
Swedish Hydroxiurea
Czech hydroxymočovina
Finnish Hydroksiurea
Russian GIDROKSIMOCHEVINA, OKSIMOCHEVINA, GIDROKSIKARBAMID, ГИДРОКСИКАРБАМИД, ГИДРОКСИМОЧЕВИНА, ОКСИМОЧЕВИНА
Japanese ヒドロキシ尿素, ヒドロキシウレア, ヒドロキシカルバシド, ヒドロキシカルバミド, ハイドレア
Spanish hidroxicarbamida (sustancia), hidroxicarbamida, hidroxiurea (producto), hidroxiurea (sustancia), hidroxiurea, Hidroxicarbamida, Hidroxiurea
Italian Idrossicarbamide, Idrossiurea
Polish Hydroksymocznik
Portuguese Hidroxiureia, Hidroxicarbamida
French Carbamoyl-hydroxylamine, Hydroxyurée
German Hydroxycarbamid, Hydroxyharnstoff
Derived from the NIH UMLS (Unified Medical Language System)

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