From the Guidelines
Hydroxyurea for sickle cell disease is typically started at 15-20 mg/kg/day as a single daily dose, with gradual increases every 8-12 weeks as tolerated to a maximum of 35 mg/kg/day. The goal is to achieve a target absolute neutrophil count of 1,500-3,000/μL and increase fetal hemoglobin levels to at least 15-20% 1. Dose adjustments should be made based on regular blood count monitoring, with temporary dose reductions or holds if neutropenia (neutrophils <1,000/μL), thrombocytopenia (platelets <80,000/μL), or severe anemia occurs. Hydroxyurea works by inducing fetal hemoglobin production, which inhibits the polymerization of sickle hemoglobin, thereby reducing sickling of red blood cells and preventing vaso-occlusive crises.
Some key points to consider when prescribing hydroxyurea include:
- Regular monitoring of complete blood counts every 2-4 weeks during dose adjustments and every 2-3 months once on a stable dose 1
- Counseling patients about potential side effects including myelosuppression, gastrointestinal symptoms, and skin changes
- Effective contraception should be used by patients of childbearing potential, as hydroxyurea is contraindicated during pregnancy
- The 2014 National Heart, Lung, and Blood Institute guidelines for SCD recommend offering hydroxyurea to every child with HbSS or Sb0-thalassemia at 9 months of age even without clinical symptoms 1
It's also important to note that hydroxyurea therapy is recommended for patients with SCD who have an increased risk for mortality, as stated in the American Thoracic Society clinical practice guideline 1. Overall, the use of hydroxyurea in sickle cell disease has been shown to have a positive impact on health-related quality of life and reduce the risk of complications such as vaso-occlusive crises and acute chest syndrome 1.
From the FDA Drug Label
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 side effects.
- Starting dose: 10-20 mg/kg/day 2, 3, 4
- Escalation dose: up to 35 mg/kg/day 2
- Maintenance dose: 15-30 mg/kg/day 4, 5
- Maximum tolerated dose (MTD): individualized, with some patients requiring up to 33 mg/kg/day 6
Considerations for Dosing
- Renal function: patients with renal impairment may require lower doses, with an initial dosing regimen of 7.5 mg/kg/day proposed for patients with CL(cr) <60 mL/min 5
- Ethnic neutropenia: requires judicious usage of myelosuppressive drugs, such as Hydroxyurea 2
- Patient monitoring: regular monitoring of platelet count, complete blood count, and Hb F is necessary to adjust Hydroxyurea dosages accordingly 3
Clinical Trials and Studies
- A study of 161 patients with SCD found that a low-dose regimen of Hydroxyurea (10-12 mg/kg/day) was effective in reducing the annual number of admissions due to vaso-occlusive crisis 2
- Another study of 10 patients with SCD found that a dose of 15 mg/kg/day was adequate for treatment, with minimal side effects and improvement in laboratory and clinical parameters 4
- A computer algorithm-based Hydroxyurea dosing study found that titration to MTD was feasible and effective in increasing fetal hemoglobin and reducing markers of organ damage 6