HYDROXYUREA

Clinical safety rating: safe

Contraindicated (not allowed)

How it works

Inhibits ribonucleotide reductase, leading to decreased DNA synthesis and cell cycle arrest in S phase; also increases fetal hemoglobin production by inducing nitric oxide and altering erythroid progenitor signaling.

What the body does with it

Metabolism	Partially metabolized by hepatic enzymes (possibly CYP450-mediated), but primarily excreted unchanged renally.
Excretion	Renal: approximately 80% (30-60% unchanged; remainder as metabolites). Fecal: <10%.
Half-life	Terminal half-life: 3.5–4.5 hours; clinical context: hematologic effects persist for 24-48 hours due to irreversible inhibition of ribonucleotide reductase.
Protein binding	Negligible (<10%); binds weakly to albumin.
Volume of Distribution	Apparent Vd: 0.5–0.8 L/kg; distributes throughout total body water.
Bioavailability	Oral: approximately 80–100% (well absorbed).
Onset of Action	Oral: cytotoxic effects on DNA synthesis begin within 24 hours; clinical reduction in white blood cell count (e.g., in chronic myeloid leukemia) typically observed within 4–7 days.
Duration of Action	Hematologic effects persist for 24–48 hours after a single dose; dosing is typically daily or every other day due to the sustained effect on rapidly dividing cells.

Classification & Brands

Dosing & administration

Oral: 15-20 mg/kg once daily (rounded to nearest 500 mg) for myeloproliferative disorders (e.g., essential thrombocythemia); 80 mg/kg every 3 days (as 35 mg/kg single dose) for sickle cell disease.

Dosage form	CAPSULE
Renal impairment	CrCl >60 mL/min: No adjustment. CrCl 30-60 mL/min: Reduce dose by 50%. CrCl 10-29 mL/min: Reduce dose by 50% and increase dosing interval to 48-72 hours. Hemodialysis: Administer after dialysis; reduce dose by 50%.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Reduce dose by 50% and monitor closely; consider alternative therapy.
Pediatric use	Sickle cell disease: Oral, 20 mg/kg once daily. Myeloproliferative disorders: Oral, 15-20 mg/kg once daily. Maximum single dose: 2000 mg. Doses rounded to nearest 500 mg.
Geriatric use	Start at lower end of dosing range (10-15 mg/kg/day) due to increased sensitivity. Monitor renal function closely; adjust dose based on CrCl. Increased risk of myelosuppression and gastrointestinal toxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

No significant drug interactions For topical use only can cause mild irritation.

Breastfeeding	Contraindicated during breastfeeding. Hydroxyurea excreted in human milk; M/P ratio not established. Potential for serious adverse effects in nursing infants (myelosuppression, carcinogenesis).
Teratogenic Risk	FDA Pregnancy Category D. First trimester: known teratogen; increased risk of fetal malformations (neural tube defects, craniofacial anomalies, skeletal defects). Second and third trimesters: risk of fetal growth restriction, bone marrow suppression, and intrauterine fetal death.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Myelosuppression: Hydroxyurea causes severe bone marrow suppression, including anemia, leukopenia, and thrombocytopenia. Monitor blood counts regularly.

Side Effect Profile

Common Effects	xerosis
Serious Effects

Absolute Contraindications

Hypersensitivity to hydroxyurea, severe bone marrow suppression (e.g., WBC < 2500/μL or platelets < 100,000/μL), pregnancy, breastfeeding (discontinue nursing).

Clinical Precautions

Precautions

Myelosuppression (dose-dependent), hemolysis in sickle cell patients, teratogenicity (Pregnancy Category D), renal impairment requires dose adjustment, increased risk of secondary malignancies (e.g., leukemia), cutaneous vasculitis and ulcers, radiation recall reaction.

Clinical Tips & Counseling

Drug interactions

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