Recommended Use and Dosage of Hydroxyurea in Patients
Hydroxyurea is recommended for sickle cell disease (SCD), polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelomonocytic leukemia (CMML), with dosing typically starting at 15 mg/kg/day for patients with normal renal function and 7.5 mg/kg/day for those with renal impairment.
Indications and Dosing by Condition
Sickle Cell Disease
- Initial dosing: 15 mg/kg/day orally once daily 1
- Titration: Can be increased to maximum tolerated dose of 25-30 mg/kg/day 1
- Target laboratory thresholds: Hemoglobin ≥9 g/dL and HbF ≥20% 1
- Efficacy: Reduces painful crises by approximately 50%, decreases acute chest syndrome episodes and blood transfusions by ~50% 2, 3
- Monitoring: Complete blood count at least weekly during initial therapy 4
Polycythemia Vera
- Indication: High-risk patients (age >60 years, history of thrombosis) or those with poor tolerance to phlebotomy 5
- Goal: Maintain hematocrit <45%, control symptoms, and reduce splenomegaly 5
- Dosing: Start at 15 mg/kg/day, adjust based on response 4
- Definition of resistance/intolerance 5:
- Need for phlebotomy despite 3 months of ≥2 g/day hydroxyurea
- Uncontrolled myeloproliferation (platelets >400×10⁹/L AND WBC >10×10⁹/L)
- Failure to reduce massive splenomegaly by >50%
- Absolute neutrophil count <1.0×10⁹/L or platelets <100×10⁹/L or hemoglobin <10 g/dL
- Presence of leg ulcers or other unacceptable toxicities
Chronic Myelomonocytic Leukemia
- Dosing: 15 mg/kg/day orally, can be titrated up to 20 mg/kg/day 5
- Continuous daily dosing: 15-50 mg/kg per day orally 5
Dose Adjustments and Monitoring
Renal Impairment
- CrCl ≥60 mL/min: 15 mg/kg once daily 4
- CrCl <60 mL/min or ESRD: 7.5 mg/kg once daily 4
- Dialysis patients: Administer following hemodialysis 4
Monitoring Requirements
- Blood counts: At least weekly during initial therapy 4
- Dose modifications: Reduce dose or discontinue for:
- Myelosuppression
- Cutaneous vasculitis
- Other toxicities 4
Administration Guidelines
- Swallow capsules whole
- Do NOT open, break, or chew capsules (cytotoxic drug)
- Prophylactic folic acid administration is recommended 4
- Severe anemia must be corrected before initiating therapy 4
Efficacy and Benefits
- In SCD: Increases hemoglobin and HbF levels, reduces painful episodes, acute chest syndrome, hospitalizations, and transfusion requirements 1, 3, 6
- In PV: Effectively controls myeloproliferation and reduces thrombotic risk 5
- In CMML: Provides cytoreduction and disease control 5
Safety Considerations
- Short-term toxicity: Generally well-tolerated 1
- Common side effects: Neutropenia, bone marrow suppression, elevated liver enzymes, anorexia, nausea, vomiting 2
- Long-term concerns: Potential fertility issues; however, no increases in stroke, myelodysplasia, or carcinogenicity have been detected in SCD patients with up to 15 years of exposure 1
Practical Considerations
- Lower doses (15 mg/kg/day) may be adequate for treatment of SCD with minimal side effects 7
- Therapeutic effects may not become apparent for several months 3
- Can be safely administered with artesunate in patients with malaria 8
Hydroxyurea represents an effective oral treatment option with documented efficacy across multiple hematologic conditions. Close monitoring is essential to balance therapeutic benefits with potential toxicities.