Hydroxyurea (Hydrocicarbamide) Dosage and Usage for Sickle Cell Disease and Cancer
For patients with sickle cell disease (SCD), hydroxyurea should be dosed at 15-35 mg/kg/day orally, with a target dose of 25-30 mg/kg/day to achieve key laboratory thresholds (Hb ≥9 g/dL and HbF ≥20%) without excessive myelosuppression. 1
Dosing for Sickle Cell Disease
Initial Dosing and Titration
- Starting dose: 15 mg/kg/day orally as a single daily dose
- Monitoring: Complete blood count (CBC) every 2-4 weeks during dose adjustment
- Dose increases: Increase by 5 mg/kg/day every 8-12 weeks if blood counts remain acceptable
- Maximum dose: 35 mg/kg/day or until mild myelosuppression occurs
- Target dose: 25-30 mg/kg/day for most patients 2, 1
Monitoring Parameters
- CBC monitoring required at baseline and regularly during treatment
- For stable doses: CBC every 1-3 months
- Target absolute neutrophil count: 2,000-4,000/μL
- Hold therapy if:
- Neutrophil count <1,000/μL
- Platelet count <80,000/μL
- Hemoglobin <4.5 g/dL
- Reticulocyte count <80,000/μL (if hemoglobin <9 g/dL) 2
Special Considerations for SCD
- In patients with SCD and chronic kidney disease with worsening anemia, combination therapy with hydroxyurea and erythropoiesis-stimulating agents is recommended 2
- For patients with SCD who have an increased risk for mortality (TRV >2.5 m/second, NT-pro-BNP >160 pg/ml, or RHC-confirmed pulmonary hypertension), hydroxyurea therapy is strongly recommended 2
- For patients with SCD with prior ischemic stroke or TIA, hydroxyurea is a reasonable alternative when chronic blood transfusions are not available or practical 2
Dosing for Cancer Indications
Resistant Chronic Myeloid Leukemia
- Initial dose: 20-30 mg/kg orally once daily
- Maintenance dose: Lowest dose that maintains white blood cell count at approximately 10,000/mm³ 3
Head and Neck Cancer
- 80 mg/kg administered orally as a single dose every third day in combination with concurrent chemoradiation
- Administer 3 hours before radiation therapy 3
Dose Adjustments
Renal Impairment
- Reduce dose by 50% in patients with creatinine clearance less than 60 mL/min 3
Hematologic Toxicity
- If bone marrow function is markedly depressed, withhold hydroxyurea until recovery
- If hemolysis persists, discontinue hydroxyurea 3
Clinical Benefits and Outcomes
Sickle Cell Disease
- Reduces frequency of painful crises by approximately 50%
- Decreases acute chest syndrome episodes by up to 80%
- Reduces hospitalizations by approximately 30%
- Reduces need for blood transfusions
- Increases total hemoglobin and fetal hemoglobin levels 1, 4, 5
Cancer
- Effective for resistant chronic myeloid leukemia
- Effective for locally advanced squamous cell carcinomas of the head and neck when used in combination with concurrent chemoradiation 3
Contraindications and Warnings
- Do not use in patients with previous hypersensitivity to hydroxyurea
- Avoid in patients with severe bone marrow depression
- Use caution in patients receiving antiretroviral therapy due to risk of pancreatitis, hepatotoxicity, and neuropathy
- Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception
- Avoid live vaccinations during treatment 3
Common Adverse Effects
- Myelosuppression (most common and dose-limiting)
- Gastrointestinal symptoms
- Anorexia
- Skin changes and nail hyperpigmentation
- Potential long-term concerns include secondary malignancies 3, 1
Implementation Barriers
Despite proven efficacy, hydroxyurea remains underutilized in SCD. Common barriers include:
- Physician concerns about carcinogenic potential
- Perceived patient apprehension about adverse effects
- Concern about contraceptive use and patient compliance
- Lack of awareness of current guidelines 6, 7
Proper education of both healthcare providers and patients about the benefits and safety profile of hydroxyurea is essential to optimize its use in clinical practice.