Hydroxyurea Indications and Dosing Guidelines
Hydroxyurea is indicated for sickle cell disease (SCD), resistant chronic myeloid leukemia, and locally advanced squamous cell carcinomas of the head and neck, with specific dosing regimens tailored to each condition. 1
Indications for Hydroxyurea
Sickle Cell Disease
- Recommended for all children with HbSS or Sβ0-thalassemia starting at 9 months of age, even without clinical symptoms 2
- Reduces frequency of painful vaso-occlusive crises, acute chest syndrome episodes, hospitalizations, and need for blood transfusions by approximately 50% 2, 3
- Increases total and fetal hemoglobin levels, which inhibits erythrocyte sickling 2
- May be used for primary stroke prevention in children with SCD who have abnormal transcranial Doppler (TCD) velocities, particularly when chronic red cell transfusions are not feasible 2
Oncologic Indications
- Treatment of resistant chronic myeloid leukemia 1
- Locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation 1
- Has been used in myeloproliferative neoplasms, although formal approval varies by country 4
Chronic Myelomonocytic Leukemia (CMML)
- First-line cytoreductive therapy for proliferative CMML with low blast counts to control proliferative myelomonocytic cells and reduce organomegaly 2
Dosing Guidelines
Sickle Cell Disease
- Initial dosing: 15-20 mg/kg/day orally as a single daily dose 2
- Can be titrated to maximum tolerated dose (MTD), typically around 25-35 mg/kg/day 5
- Available as capsules, fast-dissolving tablets, or compounded liquid 2
- For children, dosing starts at 10-15 mg/kg/day 6
Oncologic Indications
- Standard initial dose: 15 mg/kg once daily 1
- Dose should be based on patient's actual or ideal weight, whichever is less 1
- For renal impairment (CrCl <60 mL/min or ESRD): reduce dose by 50% to 7.5 mg/kg once daily 1
- On dialysis days, administer after hemodialysis 1
Monitoring Requirements
- Complete blood count (CBC) and reticulocyte count monitoring every 1-3 months depending on:
- Duration of therapy
- Stability of dose 2
- More frequent monitoring (at least weekly) during initial therapy or dose adjustments 1
- Monitor for myelosuppression, which is the most common adverse effect 1
Dose Modifications
For Toxicity
- Reduce dose or discontinue for:
For Renal Impairment
- Reduce dose by 50% if creatinine clearance is <60 mL/min 1
- For end-stage renal disease: 7.5 mg/kg once daily 1
Adverse Effects and Monitoring
Common Adverse Effects
- Myelosuppression (leukopenia is most common manifestation) 1
- Gastrointestinal symptoms (anorexia, nausea, vomiting) 3
- Skin reactions and leg ulcers 2
- Elevated liver enzymes 3
Criteria for Hydroxyurea Intolerance/Resistance
- Failure to reduce massive or progressive splenomegaly by >50% after 3 months at ≥2 g/day 2
- Uncontrolled myeloproliferation (platelets >400×109/L and WBC >10×109/L) after 3 months at ≥2 g/day 2
- Absolute neutrophil count <1.0×109/L or platelets <50×109/L at lowest effective dose 2
- Presence of leg ulcers or other unacceptable hydroxyurea-related toxicities 2
Long-term Considerations
- Potential risk of infertility, particularly relevant for younger patients 3
- Long-term safety profile continues to be studied, though evidence from BABY HUG trial showed no unique adverse effects even when initiated in early infancy and continued for more than a decade 2
Special Considerations
Combination Therapy
- In SCD patients with chronic kidney disease, combination therapy with erythropoiesis-stimulating agents may allow for more aggressive hydroxyurea dosing 2
- For head and neck cancers, used in combination with chemoradiation 1
Contraindications
- Previous hypersensitivity to hydroxyurea or any component of the formulation 1
- Markedly depressed bone marrow function (should not initiate therapy) 1