What are the indications for Hydroxyurea (Hydroxycarbamide) in Sickle Cell Disease?

From the Guidelines

Hydroxyurea is recommended for patients with sickle cell disease who experience recurrent vaso-occlusive crises, acute chest syndrome, severe symptomatic anemia, or other severe complications, and should be offered to all adults with HbSS or HbS/β0-thalassemia genotypes, and considered for children with these genotypes starting as early as 9 months of age regardless of clinical severity, as supported by the most recent guideline from the American Heart Association/American Stroke Association 1.

Key Points

• The typical starting dose is 15-20 mg/kg/day as a single daily dose, with gradual titration up to the maximum tolerated dose (usually 25-35 mg/kg/day) based on blood count monitoring.
• Hydroxyurea works by increasing fetal hemoglobin (HbF) production, reducing sickled red blood cell formation, decreasing neutrophil and platelet counts, and improving red blood cell hydration.
• These effects reduce the frequency of painful crises, acute chest syndrome, hospitalizations, and transfusion requirements while improving quality of life and potentially extending survival.
• Regular monitoring includes complete blood counts every 2-4 weeks during dose adjustment and every 2-3 months once stable, along with renal and liver function tests.
• Patients should be counseled about potential side effects including myelosuppression, gastrointestinal symptoms, and skin changes, as well as the importance of strict adherence and reliable contraception during treatment due to potential teratogenic effects.

Benefits and Risks

• The benefits of hydroxyurea therapy include reduced frequency of vaso-occlusive crises, acute chest syndrome, and hospitalizations, as well as improved quality of life and potentially extended survival 1.
• The risks of hydroxyurea therapy include myelosuppression, gastrointestinal symptoms, and skin changes, as well as potential teratogenic effects 1.

Clinical Considerations

• Hydroxyurea therapy should be individualized based on patient-specific factors, including disease severity, comorbidities, and concomitant medications.
• Regular monitoring and dose adjustments are necessary to minimize the risk of adverse effects and optimize therapeutic benefits.
• Patients with sickle cell disease should be counseled about the importance of adherence to hydroxyurea therapy and the potential risks and benefits of treatment.

From the Research

Indications of Hydroxyurea for Sickle Cell Disease

• Hydroxyurea is indicated for the treatment of sickle cell disease (SCD) to reduce the frequency of pain episodes and other acute complications 2, 3, 4.
• It is effective in increasing fetal hemoglobin (HbF) levels, which helps to reduce the severity of SCD symptoms 2, 3, 5, 4.
• Hydroxyurea may also be effective in preventing life-threatening neurological events in individuals with SCD at risk of primary stroke by maintaining transcranial Doppler velocities 2, 4.
• The medication has been shown to decrease the rate of transfusions, hospitalizations, and spleen size in patients with SCD 3.
• Hydroxyurea may be used as an alternative to blood transfusions in some cases, but the decision to switch should be made with caution, as it may increase the risk of acute chest syndrome 6.

Patient Selection

• Hydroxyurea is typically recommended for individuals with HbSS or HbSβºthal genotypes, as the evidence for its effectiveness in these populations is stronger 2, 4.
• The medication may also be considered for individuals with HbSC genotype, but the evidence is limited, and more research is needed to fully understand its effects in this population 2, 4.
• Patients who are pregnant, planning to become pregnant, or breastfeeding should use hydroxyurea with caution, as its effects on fertility and reproduction are not well understood 2, 4.

Dosage and Administration

• The typical dosage of hydroxyurea for SCD is 10-20 mg/kg/day, but the optimal dose and dosing schedule are not well established 3, 4.
• The medication should be started at a low dose and gradually increased as needed and tolerated, with regular monitoring of blood counts and other laboratory parameters 2, 4.
• Hydroxyurea can be administered orally, and it is usually taken once daily 3, 4.