Generic Name

Hydroxyurea

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Classification

FDA Approved Indications

• Chronic myelogenous leukemia (CML)
• Sickle cell disease (reduces frequency of sickling crises)
• Other myeloproliferative disorders

Mechanism of Action

Hydroxyurea inhibits ribonucleotide reductase, leading to decreased DNA synthesis, which inhibits the proliferation of rapidly dividing cells and induces fetal hemoglobin production in sickle cell disease.

Dosage and Administration

Adult: Varies by indication; for sickle cell disease, typically 15 mg/kg/day orally, adjusted based on response and tolerability.

Pediatric: Dosage individualized based on body weight and clinical response.

Geriatric: Dose adjustments may be necessary due to comorbidities and renal function.

Renal Impairment: Use with caution; dosage adjustments may be necessary.

Hepatic Impairment: Use with caution; monitor for hepatotoxicity.

Pharmacokinetics

Absorption: Well absorbed orally.

Distribution: Widely distributed in body fluids and tissues.

Metabolism: Metabolized in the liver, exact pathways not fully characterized.

Excretion: Excreted primarily in the urine.

Half Life: Approximately 3-4 hours.

Contraindications

• Hypersensitivity to hydroxyurea.
• Patients with severe myelosuppression.

Precautions

• Monitor blood cell counts regularly.
• Use with caution in pregnancy; effective contraception advised during treatment and for 6 months after.
• Patients with hepatic or renal impairment require dose adjustments and close monitoring.

Adverse Reactions - Common

• Myelosuppression (neutropenia, thrombocytopenia, anemia) (Common)
• Gastrointestinal discomfort (nausea, vomiting, diarrhea) (Common)
• Dermatologic reactions (rash, pigmentation) (Common)

Adverse Reactions - Serious

• Secondary leukemia or other secondary malignancies (Rare)
• Severe myelosuppression leading to infection or bleeding (Serious but less common)
• Hepatic toxicity (Serious, monitor liver function)

Drug-Drug Interactions

• Other myelosuppressive agents, may increase risk of hematologic toxicity.
• Clozapine, increased risk of hematologic toxicity.

Drug-Food Interactions

• No significant interactions noted.

Drug-Herb Interactions

• Limited data, caution advised with herbs that affect blood counts.

Nursing Implications

Patient/Family Teaching

• Report signs of infection promptly.
• Use effective contraception.
• Follow-up blood tests as scheduled.
• Avoid pregnancy during and for 6 months after therapy.

Special Considerations

Black Box Warnings:

• Potential for secondary malignancies such as leukemia.
• Severe myelosuppression leading to infection or bleeding.

Genetic Factors: Not specifically associated with genetic factors affecting drug metabolism.

Lab Test Interference: May alter blood counts, need to distinguish drug effects from disease progression.

Overdose Management

Signs/Symptoms: Severe myelosuppression, bleeding, infection.

Treatment: Supportive care, transfusions if necessary, colony-stimulating factors, hospitalization.

Storage and Handling

Storage: Store at controlled room temperature 20°C to 25°C (68°F to 77°F).

Stability: Stable if unopened for the duration of the shelf life as per manufacturer.