HYDROXYUREA
Clinical safety rating: safe
Contraindicated (not allowed)
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.
| 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. |
| Molecular Weight | 76.05 |
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. |
| 1st trimester | Contraindicated in first trimester due to teratogenicity; avoid unless benefit outweighs risk in life-threatening disease. |
| 2nd trimester | Avoid in second trimester; known to cause fetal harm, including growth restriction and malformations. |
| 3rd trimester | Avoid in third trimester; risk of neonatal myelosuppression, pancytopenia, and fetal anemia. |
Clinical note
No significant drug interactions For topical use only can cause mild irritation.
| Placental transfer | Crosses placenta; fetal serum levels similar to maternal levels. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants, including myelosuppression and carcinogenesis. Discontinue nursing or drug based on maternal need. |
■ FDA Black Box Warning
Myelosuppression: Hydroxyurea causes severe bone marrow suppression, including anemia, leukopenia, and thrombocytopenia. Monitor blood counts regularly.
| Common Effects | xerosis |
| Serious Effects |
Bone marrow depression (severe anemia, leukopenia, thrombocytopenia)PregnancyHypersensitivity to hydroxyurea
| 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. |
| Food/Dietary | No specific food interactions are reported, but it is recommended to take hydroxyurea with food to reduce gastrointestinal upset. Avoid grapefruit juice? No clinically relevant interaction; however, patients should maintain adequate hydration. Alcohol consumption should be limited due to potential hepatotoxicity and pancreatitis risk, especially in patients with sickle cell disease. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| 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 | Complete blood count (CBC) every 2–4 weeks; liver and renal function tests monthly; fetal ultrasound for growth and anomalies; maternal serum alpha-fetoprotein screening; amniocentesis if indicated; monitor for signs of infection. |
| Fertility Effects | May impair fertility in both sexes. Reversible azoospermia or oligospermia in males. Females: possible ovarian suppression, amenorrhea, and premature ovarian failure. Fertility preservation consultation recommended. |
| Clinical Pearls | Hydroxyurea is an S-phase-specific antimetabolite that inhibits ribonucleotide reductase, leading to cell cycle arrest at G1/S phase. It is used in myeloproliferative neoplasms (e.g., essential thrombocythemia, polycythemia vera) and sickle cell disease. Monitor for myelosuppression, particularly neutropenia and thrombocytopenia; dose adjustments may be needed based on ANC. Contraindicated in pregnancy (teratogenic) and breastfeeding. Watch for leg ulcers and skin changes (e.g., dermatomyositis-like rash). Hydroxyurea increases fetal hemoglobin (HbF) in sickle cell disease by inhibiting DNA synthesis in erythroid precursors. Avoid concurrent use with didanosine or stavudine due to increased risk of peripheral neuropathy and pancreatitis. |
| Patient Advice | Take hydroxyurea exactly as prescribed, usually once daily. Do not crush or chew capsules; swallow whole. If you miss a dose, take it as soon as remembered unless it is almost time for the next dose; do not double up. · Hydroxyurea can lower your blood cell counts, so you will need regular blood tests to monitor. Notify your doctor immediately if you develop fever, signs of infection, unusual bruising or bleeding, or fatigue. · This medication can cause birth defects; do not become pregnant or father a child while on treatment. Use effective contraception during therapy and for at least 6 months after stopping. Avoid breastfeeding. · You may experience side effects such as nausea, loss of appetite, or mouth sores. Take with food to reduce stomach upset. Report any severe or persistent symptoms. · Drink plenty of fluids to stay hydrated, especially if you have sickle cell disease. Avoid alcohol as it may increase the risk of liver problems or pancreatitis. · Your urine may appear red or orange; this is normal and harmless. Contact your doctor if you develop skin ulcers or a rash, especially on sun-exposed areas; use sun protection. · Keep all appointments for blood tests and follow-up visits. Do not stop taking this medication without consulting your doctor, as it may cause a sudden increase in blood counts or sickle cell crises. |