What is the recommended dosage of hydroxyurea (hydroxycarbamide) for sickle cell disease (SCD)?

Hydroxyurea Dosing Recommendations for Sickle Cell Disease

Hydroxyurea should be initiated at 15-20 mg/kg/day as a single daily dose and titrated up to 25-35 mg/kg/day as the maximum tolerated dose (MTD) based on laboratory monitoring, with dose adjustments to achieve optimal clinical benefits while avoiding myelosuppression. 1, 2, 3

Initial Dosing and Administration

• Hydroxyurea is taken once daily orally and is available as capsules, fast-dissolving tablets, or compounded liquid formulations 4
• Starting dose typically ranges from 15-20 mg/kg/day for both children and adults 2, 3
• For very young children (<18 months), pharmacokinetically guided dosing may allow for higher initial doses (approximately 27-28 mg/kg/day) with more rapid achievement of clinical benefits 3

Dose Titration and Maximum Dosing

• Dose should be gradually increased by 2.5-5.0 mg/kg increments every 8 weeks as tolerated 1
• Target maximum tolerated dose (MTD) typically ranges from 25-35 mg/kg/day 1, 3
• MTD is defined as the dose that produces mild myelosuppression without severe toxicity 1
• The average effective dose in clinical practice is approximately 20-30 mg/kg/day 2, 5

Monitoring Requirements

• Complete blood count (CBC) with reticulocyte count should be monitored:
  • Every 2-4 weeks during initial dose titration 4
  • Every 1-3 months once on stable dose, depending on duration of therapy and dose stability 4
• Dose-limiting toxicity is primarily myelosuppression, which typically resolves within 2 weeks of temporary discontinuation 4
• After temporary discontinuation due to toxicity, therapy can be resumed at a lower dose 4

Special Populations

• Children as young as 9 months of age with HbSS or Sβ0-thalassemia should be offered hydroxyurea even without clinical symptoms 4
• For patients with sickle cell disease and chronic kidney disease with worsening anemia, combination therapy with erythropoiesis-stimulating agents may allow for more aggressive hydroxyurea dosing 6
• When using combination therapy with erythropoiesis-stimulating agents, hemoglobin levels should not exceed 10 g/dL to reduce risk of vaso-occlusive complications 6

Expected Clinical and Laboratory Responses

• Laboratory improvements typically include:
  • Increased hemoglobin (from baseline ~7-8 g/dL to 8.5-10 g/dL) 1, 3
  • Increased fetal hemoglobin (HbF) from baseline ~3-11% to 23-33% 1, 2, 3
  • Decreased white blood cell count and neutrophil count 1, 2
  • Increased mean corpuscular volume (MCV) 2, 5
• Clinical benefits include reduced:
  • Vaso-occlusive pain episodes 1
  • Acute chest syndrome events 1
  • Hospitalizations 1, 5, 7
  • Transfusion requirements 1
  • Infection rates 1, 7

Common Pitfalls and Caveats

• Myelosuppression is the most common adverse effect but is typically manageable with dose adjustments 4
• Full clinical benefits may take several months to achieve, especially with traditional dose escalation approaches 3
• Adherence to medication and monitoring schedule is critical for achieving optimal outcomes 4
• Hydroxyurea is not associated with increased risk of birth defects, infection, stroke, or neoplasia in long-term follow-up studies 4
• Pharmacokinetically guided dosing approaches may achieve faster and more robust clinical responses compared to traditional weight-based dosing 3