II. Mechanism: Sickle Cell Anemia
- Increases production of fetal Hemoglobin (HbF) which does not sickle
III. Indications: Sickle Cell Anemia
- Indications in adults
- Sickle Cell Crisis 3 or more times in 12 months
- Severe or recurrent Acute Chest Syndrome
- Severe symptomatic chronic Anemia affecting functional status
- Sickle cell associated pain significantly impacting function or quality of life
- Indications in children over age 9 months
- All children over age 9 months should be offered Hydroxyurea to reduce complications
IV. Contraindications
- Pregnancy
- Lactation
V. Monitoring
- Baseline
- Complete Blood Count with differential
- Reticulocyte Count
- Hemoglobin F quantitative measurement
- Comprehensive metabolic panel (Renal Function tests, Liver Function Tests)
- Pregnancy Test
- Labs while adjusting dose (every 4 weeks or more)
- Reticulocyte Count
- Complete Blood Count with differential and platelets
- Maintain Absolute Neutrophil Count (ANC) > 2,000/mm3
- Maintain Platelet Count >80,000/mm3
- Labs when cytopenia occurs (every 1 week)
- Reticulocyte Count
- Complete Blood Count with differential and platelets
- Periodic labs when on stable dose (every 2-3 months)
- Reticulocyte Count
- Complete Blood Count with differential and platelets
- Hemoglobin F quantitative measurement may be obtained to evaluate for response
VI. Management
- Often managed in conjunction with Sickle Cell Disease specialist
- Trial for minimum of 6 months before assessing efficacy
- Encourage compliance for maximal effect
- Starting Doses
- Obtain baseline labs as above prior to initiating Hydroxyurea
- Arrange reliable Contraception for while on Hydroxyurea
- Dosing: Infants and Children
- Hydroxyurea 20 mg/kg daily
- Dosing: Adults with normal Renal Function
- Hydroxyurea 15 mg/kg (round up to nearest 500 mg) daily
- Dosing: Adults with Chronic Kidney Disease
- Hydroxyurea 5-10 mg/kg daily
- Adjusting dose
- See lab monitoring as above
- Maximum daily dose: 35 mg/kg/day
- Decreasing dose
- Indications
- Neutropenia (ANC <2000/mm3)
- Thrombocytopenia (Platelet Count <80,000/mm3)
- Approach
- Consult with specialist
- In some infants and children, ANC >1250/mm3 (instead of 2000/mm3) may be acceptable
- Increase lab monitoring to weekly as above
- Reduce Hydroxyurea dose by 5 mg/kg/day
- Indications
- Increasing dose
- Target ANC 2000 to 4000/mm3
- Increase by 5 mg/kg/day increments every 8 weeks
VII. Efficacy
- Full benefits may not be seen for the first 6 months after starting Hydroxyurea
- Reduces Sickle Cell Anemia mortality and hospitalizations (fewer episodes of crisis and Acute Chest Syndrome)
- Reduces Sickle Cell Crisis by 50%
- Steinberg (2003) JAMA 289:1645-51 [PubMed]
VIII. Resources
- NIH: NHLBI Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014
IX. References
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| hydroxyurea (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| HYDROXYUREA 500 MG CAPSULE | Generic | $0.32 each |
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 |
