Generic Name

Hydrea

Brand Names

for hydroxyurea, a cytotoxic oral agent widely used in hematology and oncology to inhibit DNA synthesis by targeting ribonucleotide reductase.

Mechanism

• Ribonucleotide reductase inhibitor – hydroxyurea reduces the deoxyribonucleotide pool, limiting DNA synthesis.
• Oxidative stress induction – generates reactive oxygen species that damage rapidly dividing cells.
• Blood cell modulation – in sickle cell disease it increases fetal hemoglobin (HbF) and reduces red‑cell sickling.

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Pharmacokinetics

• Absorption – ~70–90 % oral bioavailability; peak plasma concentration 2–4 h after dosing.
• Distribution – widely distributed; penetrates bone marrow, spleen, and CNS.
• Metabolism – minimal hepatic metabolism; largely excreted unchanged in urine.
• Half‑life – 5–10 h (variable with renal function).
• Renal clearance – 75–85 % cleared via glomerular filtration; dose adjusted for creatinine clearance < 50 ml/min.

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Indications

• Sickle Cell Disease – decrease vaso‑occlusive crises, reduce blood transfusions.
• Polycythemia Vera (PV) – reduce hematocrit, leucocytosis, and splenomegaly.
• Myelofibrosis & Myelodysplastic Syndromes – near‑median‑life‑saver for intermediate‑2 risk patients.
• Acute Myeloid Leukemia (AML) – as adjunct therapy in low‑risk or relapsed cases.
• Chronic Myelogenous Leukemia (CML) – when tyrosine‑kinase inhibitors fail.

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Contraindications

• Absolute
• Hypersensitivity to hydroxyurea or thalidomide.
• Pregnancy (teratogenic) and lactation.
• Relative
• Severe myelosuppression (ANC < 1 × 10⁹/L, platelets < 50 × 10⁹/L).
• Renal failure (eGFR  5 × ULN).
• Warnings
• Monitor for skin lesions (ulceration, hyperpigmentation).
• Potential for secondary malignancies with long‑term use.
• Cytopenias can precipitate infection or hemorrhage.

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Dosing

| AML (combination) | 7 days of 200 mg/m² i.v. (Day 1–7) | Cross‑over to oral if tolerated | 200 mg/m² | D1–7; then daily**
• Administration – oral capsules swallowed whole; tablets may be crushed if necessary.
• Monitoring – CBC every 2–4 weeks during dose escalation.

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Adverse Effects

Common (≥ 10 %)
• Nausea & vomiting
• Anemia, leukopenia, thrombocytopenia
• Alopecia
• Skin rashes & hyperpigmentation

Serious (≤ 5 %)
• Severe neutropenia → febrile neutropenia
• Primary thrombosis or hemorrhage
• Severe mucositis
• Therapy‑related neoplasms (e.g., squamous cell carcinoma)

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Monitoring

• Complete Blood Count (CBC) – every 2–4 weeks initially; then monthly.
• Differential (ANC) – ensure > 1 × 10⁹/L.
• Renal Function – serum creatinine, eGFR at baseline and quarterly.
• Liver Enzymes – AST/ALT baseline, then every 3 months.
• Fetal Hemoglobin Levels – q3‑6 months in SCD.
• Clinical Signs – skin lesions, infections, bleeding events.

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Clinical Pearls

• Sickle Cell Titration – start low; patient‑specific adjustment is crucial. In pediatric patients, dose conversion to mg/kg reduces overdosing risk.
• Polycythemia Vera – use *Incremental Monitoring*; ramp up 500 mg increments while keeping hematocrit below 45 %.
• Myelofibrosis – maintain *platelet count* above 80 × 10⁹/L to avoid thrombosis; if < 50 × 10⁹/L, reduce dose or add transfusion support.
• Renal Impairment Handling – halve dose if eGFR 30–50 ml/min; avoid if < 30 ml/min.
• Dermatologic Safeguard – routine skin exams; prompt biopsy of suspicious lesions (especially in long‑term users).
• Drug‑Drug Interactions – *Cimetidine* may reduce renal clearance; consider dose adjustment.
• Vaccination Strategy – give revaccinations for CDC‑recommended adult vaccines (influenza, pneumococcal) before therapy due to immune compromise.
• Patient Education – instruct to report fever, sore throat, or unusual bleeding immediately; counseling on contraception, especially for women of childbearing age.

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• Hydrea remains a cornerstone drug in managing various myeloproliferative and hematologic disorders, balancing cytoreduction with careful monitoring to mitigate toxicities.