What is the proper use and dosage of Hydroxyurea (Hydrea) injection in a patient with chronic myeloid leukemia (CML) or sickle cell disease, considering their renal function and potential need for close medical supervision?

Hydroxyurea in CML and Sickle Cell Disease: Proper Use and Dosing

Hydroxyurea injection is not a standard formulation—hydroxyurea is administered orally as capsules, fast-dissolving tablets, or compounded liquid formulations, not as an injection. 1, 2

Clinical Indications and Role

Chronic Myeloid Leukemia (CML)

Hydroxyurea serves only as temporary bridging therapy in CML at 40 mg/kg/day orally before BCR-ABL1 confirmation, particularly when high leukocyte counts or clinical symptoms require immediate intervention. 3

• Taper hydroxyurea before discontinuation once tyrosine kinase inhibitor (TKI) therapy begins immediately after BCR-ABL1 positivity is confirmed. 3
• In hyperleukocytosis (leukocytes >100 × 10⁹/L), use doses up to 50-60 mg/kg/day until leukocytes decrease to <10-20 × 10⁹/L. 1, 4
• Hydroxyurea is not definitive therapy for CML—TKIs are the cornerstone of treatment. 3

Sickle Cell Disease (SCD)

For sickle cell disease, initiate hydroxyurea at 15-20 mg/kg/day orally once daily, then titrate to maximum tolerated dose of 20-35 mg/kg/day based on hematologic response. 1, 2

• Children as young as 9 months with HbSS or Sβ0-thalassemia should receive hydroxyurea even without clinical symptoms. 1, 2
• Hydroxyurea reduces vaso-occlusive crises, acute chest syndrome, hospitalizations, and transfusions by approximately 50%. 5, 6
• Prolonged therapy (≥5 years) is necessary to achieve mortality benefit. 1

Monitoring Requirements

For Sickle Cell Disease

• Monitor complete blood count (CBC) with reticulocyte count every 2-4 weeks during initial dose titration. 2, 5
• Once on stable dose, monitor every 1-3 months depending on duration of therapy and dose stability. 2

Managing Myelosuppression

• Myelosuppression is the primary dose-limiting toxicity but typically resolves within 2 weeks of temporary discontinuation. 1, 2
• If severe myelosuppression occurs (decrease in one or more cell lines), temporarily suspend hydroxyurea. 1
• Resume therapy at a lower dose once counts recover. 2, 5
• Mild to moderate neutropenia (47% of patients) requires dose reduction but not discontinuation. 1

Renal Function Considerations

For patients with chronic kidney disease and progressive anemia on hydroxyurea, consider combined therapy with erythropoiesis-stimulating agents (ESAs), but maintain hemoglobin ≤10 g/dL to reduce risk of vaso-occlusive complications, stroke, and venous thromboembolism. 3, 1

• ESAs allow more aggressive hydroxyurea dosing by counteracting treatment-related anemia. 3, 1
• The hemoglobin ceiling of ≤10 g/dL prevents hyperviscosity complications. 3, 1
• Only 1 of 56 patients (1.8%) experienced worsening SCD symptoms with combination therapy. 3

Tumor Lysis Syndrome Prevention (CML Context)

To avoid tumor lysis syndrome when initiating hydroxyurea for CML, recommend 2.5-3 L fluid intake daily, considering individual cardiac and renal status. 3

• Sodium bicarbonate may be used to set urine pH to 6.4-6.8 for optimal uric acid clearance. 3
• Restrict allopurinol to patients with symptomatic hyperuricemia only, as it may increase risk of xanthine accumulation with renal failure. 3

Common Pitfalls and Caveats

Formulation Confusion

• There is no injectable hydroxyurea formulation—only oral preparations exist. 1, 2
• Available as capsules, fast-dissolving tablets, or compounded liquid. 1, 2, 5

Long-term Safety

• Long-term follow-up studies show no increased risk of birth defects, infection, stroke, or neoplasia in sickle cell disease. 2, 5
• However, mucocutaneous changes (leg ulcers, skin atrophy, hyperpigmentation) occur in approximately 13% of patients with long-term use in myeloproliferative disorders. 7
• Rare case reports of acute myeloid leukemia exist, though leukemogenic risk in benign hematological conditions remains undefined. 8

Drug Interactions

• Do not suspend hydroxyurea when initiating doxycycline or other antibiotics. 1
• Suspend hydroxyurea ≥72 hours before CAR-T cell infusion if patient is on transplant protocol. 1

Clinical Response Timeline

• Benefits do not become manifest for several months—expect median time to first crisis of 3.0 months in responders. 6
• Maximal tolerated doses may not be necessary to achieve therapeutic effect. 6