What is the recommended dose of Hydroxyurea (Hydroxycarbamide) for Sickle Cell Disease?

From the Guidelines

Hydroxyurea for sickle cell disease is typically started at 15-20 mg/kg/day as a single daily dose, with gradual titration based on response and tolerability. The maximum dose is usually 35 mg/kg/day, though most patients respond at 20-30 mg/kg/day. Dose adjustments should occur every 8-12 weeks with monitoring of complete blood counts, as recommended by the National Heart, Lung, and Blood Institute guidelines for SCD 1. The goal is to achieve a fetal hemoglobin (HbF) level of at least 15-20% and an absolute neutrophil count of 2,000-4,000/μL. Patients should be monitored for potential side effects including myelosuppression, with regular blood count checks every 2-4 weeks during dose adjustments and every 2-3 months once stable. Hydroxyurea works by increasing fetal hemoglobin production, reducing sickle hemoglobin polymerization, and decreasing painful crises. It also reduces white blood cell adhesion to vessel walls and improves red blood cell hydration. Treatment is long-term, and benefits typically emerge after 3-6 months of consistent use. Patients should be counseled about the importance of daily adherence, potential side effects, and the need for contraception during treatment due to potential teratogenic effects. The use of hydroxyurea in SCD has been supported by strong recommendations and moderate-quality evidence, as seen in the American Thoracic Society clinical practice guideline 1.

Some key points to consider when prescribing hydroxyurea for SCD include:

• Starting dose: 15-20 mg/kg/day
• Maximum dose: 35 mg/kg/day
• Dose adjustments: every 8-12 weeks
• Monitoring: complete blood counts every 2-4 weeks during dose adjustments and every 2-3 months once stable
• Goal: achieve a fetal hemoglobin (HbF) level of at least 15-20% and an absolute neutrophil count of 2,000-4,000/μL
• Potential side effects: myelosuppression, teratogenic effects
• Benefits: increased fetal hemoglobin production, reduced sickle hemoglobin polymerization, decreased painful crises, improved red blood cell hydration.

From the FDA Drug Label

Reduce the dose of hydroxyurea capsules when it is administered to patients with creatinine clearance of <60 mL/min or with ESRD following hemodialysis [see Dosage and Administration (2.3) and Use in Specific Populations (8. 6)].

The FDA drug label does not answer the question.

From the Research

Recommended Dose of Hydroxyurea for Sickle Cell Disease

The recommended dose of Hydroxyurea (Hydroxycarbamide) for Sickle Cell Disease varies depending on the patient's response and tolerance to the medication.

• Starting dose: 15-20 mg/kg/day, which can be escalated up to 35 mg/kg/day 2
• Low-dose regimen: 10-12 mg/kg/day, adjusted based on response or side effects, has been shown to be effective and safe in some studies 2, 3
• Minimal dose: 15 mg/kg/day has been suggested as an adequate dose for treatment of sickle cell disease, considering minimal side effects and improvement in laboratory and clinical parameters 4

Special Considerations

• Renal function: patients with renal impairment may require a lower initial dose, such as 7.5 mg/kg/day, to avoid increased systemic exposure and decreased urinary recovery 5
• Maximum tolerated dose: titration to maximum tolerated dose, which can be facilitated by a computer algorithm-based dosing program, has been shown to be effective in increasing fetal hemoglobin levels and reducing disease-related complications 6

Key Findings

• Low-dose regimens of Hydroxyurea have been shown to be effective in reducing vaso-occlusive crisis and transfusion requirements in adult HbSS patients 3
• Hydroxyurea dose escalation should be cautious and based on patient response and tolerance to the medication 2, 4