Hydroxyurea

• Approved Indications
• Hematologic Disorders:
• Sickle Cell Disease (SCD): Reduces frequency of painful crises and need for blood transfusions in adults and children with moderate to severe SCD.
• Chronic Myelogenous Leukemia (CML): As cytoreductive therapy to control elevated white blood cell counts.
• Polycythemia Vera: To reduce elevated hematocrit and risk of thrombotic events.
• Essential Thrombocythemia: For patients at high risk of thrombotic complications.
• Other Malignancies: Occasionally used in head and neck squamous cell carcinoma or other off-label malignancies under specialist supervision.
• Off-label / Clinically Accepted Uses
• Myeloproliferative disorders not otherwise specified.
• Adjunctive therapy in HIV infection for reducing viral replication in certain research contexts.

• Sickle Cell Disease (Adults & Children ≥2 years)
• Starting dose: 15 mg/kg orally once daily
• Titration: Increase by 5 mg/kg every 8–12 weeks based on hematologic response and tolerability
• Maximum recommended dose: 35 mg/kg/day
• Chronic Myelogenous Leukemia / Myeloproliferative Disorders
• Typical starting dose: 15–20 mg/kg/day orally, adjust based on blood counts
• Elderly / Renal or Hepatic Impairment
• Caution advised; consider lower initial doses and frequent monitoring
• Administration
• Oral capsules or tablets, with or without food
• Maintain hydration to reduce risk of renal toxicity

Hydroxyurea is a ribonucleotide reductase inhibitor, which blocks the conversion of ribonucleotides to deoxyribonucleotides, thereby inhibiting DNA synthesis in rapidly dividing cells. In sickle cell disease, hydroxyurea induces fetal hemoglobin (HbF) production, reducing the proportion of sickle hemoglobin (HbS), which improves red blood cell deformability and reduces vaso-occlusive crises. In myeloproliferative disorders, it suppresses excessive myeloid proliferation, helping to normalize blood counts and prevent thrombotic complications.

• Absorption: Rapid oral absorption; peak plasma concentration 1–4 hours post-dose
• Bioavailability: Approximately 80–100%
• Distribution: Widely distributed; crosses placenta and enters CSF at low levels
• Metabolism: Partial hepatic metabolism; spontaneous decomposition also occurs
• Active Metabolites: Minimal; main effects due to parent compound
• Excretion: Primarily renal; half-life 3–4 hours
• Onset of Action: Hematologic response may take 2–6 weeks; HbF induction may require 3–6 months

• Pregnancy: Category D; associated with teratogenicity and fetal harm. Should only be used if benefits outweigh risks.
• Lactation: Not recommended; excreted in breast milk, potential risk to infant.
• Caution: Effective contraception required for both male and female patients during therapy and for at least 6 months after discontinuation.

• Primary Class: Antineoplastic / Cytoreductive agent
• Subclass: Antimetabolite (Ribonucleotide reductase inhibitor)

• Known hypersensitivity to hydroxyurea or formulation excipients
• Severe bone marrow suppression (e.g., baseline neutrophils <2 × 10⁹/L)
• Active infection with significant immunosuppression
• Pregnancy or breastfeeding unless clearly justified by a specialist

• Bone Marrow Suppression: Monitor CBC weekly initially, then every 2–4 weeks
• Teratogenicity: Use effective contraception
• Renal or Hepatic Impairment: Dose adjustments required; monitor organ function
• Secondary Malignancies: Rare cases of leukemia reported with long-term use
• Gastrointestinal Toxicity: Monitor for ulcers or mucositis
• High-risk Groups: Elderly, immunocompromised, or pre-existing marrow disorders

• Hematologic:
• Neutropenia, anemia, thrombocytopenia
• Gastrointestinal:
• Nausea, vomiting, diarrhea, mucositis
• Dermatologic:
• Rash, hyperpigmentation, nail changes, alopecia
• Other:
• Headache, fever, fatigue
• Serious / Rare:
• Secondary leukemia, pulmonary fibrosis (very rare)
• Onset: Hematologic effects usually within 2–6 weeks; other effects variable

• Additive myelosuppressive drugs (e.g., azathioprine, methotrexate) → increased risk of cytopenias
• Live vaccines: Avoid during treatment due to immunosuppression
• No significant CYP450 interactions; primarily metabolized spontaneously and renally excreted
• Alcohol may increase risk of myelosuppression indirectly

• Sickle Cell Disease: Current guidelines recommend early initiation in children ≥9 months to prevent complications
• Monitoring: Emphasis on regular CBC and organ function monitoring for dose adjustments
• Malignancy Use: Remains a standard cytoreductive therapy for myeloproliferative disorders
• No major changes in FDA-approved indications recently; guidelines highlight HbF induction and prevention of vaso-occlusive crises as primary benefit

• Temperature: Store at 20°C–25°C (room temperature)
• Light & Humidity: Protect from moisture and light
• Handling: Use gloves when handling powdered forms; avoid inhalation
• Reconstitution: Not applicable for capsules/tablets; oral solution formulations must be used as directed