What are the contraindications for hydroxyurea?

Contraindications for Hydroxyurea

Hydroxyurea is contraindicated in patients with previous hypersensitivity to hydroxyurea or any other component of its formulation, and should not be initiated in patients with markedly depressed bone marrow function. 1

Absolute Contraindications

• Previous hypersensitivity to hydroxyurea or any component of the formulation 1
• Markedly depressed bone marrow function 1

Relative Contraindications and Cautions

Hematologic Considerations

• Severe anemia (must be corrected before initiating therapy) 1
• Leukopenia, thrombocytopenia (monitor CBC at least weekly) 1
• Hemolytic anemia (discontinue if diagnosed) 1, 2

Renal Considerations

• Severe renal impairment (requires 50% dose reduction for creatinine clearance <60 mL/min or ESRD) 1

Dermatologic Considerations

• History of cutaneous vasculitic toxicities (especially in patients with history of interferon therapy) 1
• Leg ulcers (discontinue if they develop) 3

Special Populations

• Pregnancy (contraindicated due to embryo-fetal toxicity) 1
• Young patients (<40 years) - use with caution due to potential long-term risks 3
• Patients planning to receive live vaccines (avoid concurrent use) 1

Intolerance Criteria

Hydroxyurea should be discontinued if any of these develop:

For Polycythemia Vera:

1. Need for phlebotomy to keep hematocrit <45% despite 3+ months of hydroxyurea ≥2g/day 3
2. Uncontrolled myeloproliferation (platelet count >400×10⁹/L AND WBC >10×10⁹/L) despite 3+ months of hydroxyurea ≥2g/day 3
3. Failure to reduce massive splenomegaly by >50% or relieve splenomegaly symptoms after 3+ months of hydroxyurea ≥2g/day 3
4. Cytopenias at lowest effective dose:
   • Absolute neutrophil count <1.0×10⁹/L
   • Platelet count <100×10⁹/L
   • Hemoglobin <10 g/dL 3
5. Mucocutaneous manifestations (including leg ulcers) 3
6. GI symptoms, pneumonitis, or fever at any dose 3

For Essential Thrombocythemia:

1. Platelet count >600×10⁹/L after 3+ months of hydroxyurea ≥2g/day 3
2. Platelet count >400×10⁹/L with hemoglobin <10 g/dL at any dose 3
3. Mucocutaneous manifestations (including leg ulcers) 3
4. Hydroxyurea-related fever 3

Monitoring Requirements

• Complete blood count at least weekly during initial therapy 1
• Renal function tests periodically 4
• Monitor for signs of hemolysis (jaundice, hematuria, elevated LDH, decreased haptoglobin) 1, 2
• Skin examination for ulcers, vasculitic lesions, and malignancies during long-term therapy 1

Clinical Pitfalls to Avoid

1. Not recognizing hemolytic anemia: Not all hydroxyurea-induced anemia is due to bone marrow suppression; hemolysis can occur and requires drug discontinuation 1, 2

2. Inadequate monitoring: Weekly blood count monitoring is essential during initial therapy to avoid severe myelosuppression 1

3. Overlooking secondary malignancy risk: Long-term use is associated with increased risk of secondary leukemia and skin cancer; monitor accordingly 1

4. Ignoring renal function: Failure to adjust dose in renal impairment can lead to excessive toxicity 1

5. Concomitant live vaccines: Avoid administration of live vaccines during hydroxyurea therapy due to potential for increased viral replication and/or adverse reactions 1

By following these guidelines and monitoring parameters, clinicians can safely administer hydroxyurea while minimizing adverse effects and optimizing outcomes for patients with myeloproliferative disorders, sickle cell disease, and other indicated conditions.