DROXIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DROXIA (DROXIA).
Hydroxyurea inhibits ribonucleotide reductase, depleting deoxyribonucleotides and inducing fetal hemoglobin (HbF) synthesis.
| Metabolism | Partially hepatic (via glucuronidation) and partially renal; about 50% excreted unchanged in urine. |
| Excretion | Renal: approximately 50% of absorbed dose excreted unchanged in urine. Biliary/fecal: up to 20% excreted in feces as metabolites, with less than 5% as unchanged drug. |
| Half-life | 3–4 hours in patients with normal renal function; prolonged to 8–12 hours in moderate to severe renal impairment (CrCl <30 mL/min), requiring dose adjustment. |
| Protein binding | Negligible (<5%); does not significantly bind to plasma proteins. |
| Volume of Distribution | 0.5–1.0 L/kg; distributes widely into total body water, including red blood cells (concentrates in erythroid precursors). |
| Bioavailability | ~80% after oral administration, with rapid absorption (peak plasma concentration at 0.5–2 hours). Food decreases absorption by ~20%. |
| Onset of Action | Oral: 24–48 hours for reduction in elevated hematocrit in polycythemia vera; 7–14 days for reduction in platelet count in essential thrombocythemia. |
| Duration of Action | Approximately 24 hours; requires continuous daily dosing to maintain cytoreductive effect. Effect on blood counts lasts 7–10 days after discontinuation. |
Hydroxyurea (Drosia) for sickle cell anemia: Oral, starting dose 15 mg/kg once daily; escalate by 5 mg/kg every 12 weeks to maximum 35 mg/kg/day. For essential thrombocythemia: 15-30 mg/kg once daily. For myelodysplastic syndrome: 15-30 mg/kg once daily.
| Dosage form | CAPSULE |
| Renal impairment | For CrCl <30 mL/min: reduce dose by 50%. For CrCl <10 mL/min: use has not been studied; consider alternative therapy. |
| Liver impairment | Child-Pugh Class B: reduce starting dose by 50% and titrate cautiously. Child-Pugh Class C: avoid use due to lack of data. |
| Pediatric use | Children (≥2 years) with sickle cell anemia: initial 15 mg/kg once daily, increase by 5 mg/kg every 8-12 weeks to max 35 mg/kg/day. No data for other indications. |
| Geriatric use | Start at the lower end of dosing range (15 mg/kg), monitor renal function closely; consider dose adjustment based on CrCl and tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DROXIA (DROXIA).
| Breastfeeding | Hydroxyurea is excreted into human milk; M/P ratio not established. Breastfeeding is contraindicated due to potential for serious adverse reactions in the infant (e.g., bone marrow suppression, carcinogenicity). |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: Hydroxyurea is teratogenic in animals; human data limited but avoid use. Second/third trimesters: Potential fetal harm including growth restriction, anemia, and congenital anomalies; use only if clearly needed and no safer alternatives. |
| Fetal Monitoring |
■ FDA Black Box Warning
Hydroxyurea is carcinogenic and mutagenic. Severe myelosuppression may occur.
| Serious Effects |
["Severe bone marrow suppression (e.g., WBC <2500/μL, platelets <100,000/μL)","Hypersensitivity to hydroxyurea","Pregnancy (teratogenic)","Breastfeeding (excreted in milk)"]
| Precautions | ["Myelosuppression (monitor CBC regularly)","Secondary leukemia (especially with long-term use)","Macrocytosis (common, not indicative of B12/folate deficiency)","Hydroxyurea embryofetal toxicity (pregnancy Category D)","Vaccination modifications (avoid live vaccines)"] |
| Food/Dietary | Avoid alcohol. No specific food restrictions, but maintain adequate hydration. Take with food if gastrointestinal upset occurs. |
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| Monitor CBC with differential, platelets, and renal function at baseline and monthly. Assess for fetal growth (ultrasound) and consider fetal echocardiography if used in pregnancy. Monitor for maternal myelosuppression. |
| Fertility Effects | Hydroxyurea may impair fertility in males (oligospermia, azoospermia) and females (amenorrhea); effects may be reversible upon discontinuation. |
| Clinical Pearls | Hydroxyurea (DROXIA) is primarily used for sickle cell disease to reduce painful crises and acute chest syndrome. Monitor CBC every 2 weeks initially, then monthly. Dose adjustments are based on ANC (target >2000/μL) and platelet count. Avoid in pregnancy and breastfeeding. May cause macrocytosis, which is a desired effect in sickle cell. Contraindicated with severe bone marrow suppression. Start at 15 mg/kg/day, increase by 5 mg/kg/day every 12 weeks if tolerated. Maximum dose 35 mg/kg/day. |
| Patient Advice | Take exactly as prescribed; do not stop without consulting your doctor. · This medication can lower your blood counts, increasing infection and bleeding risk. Report fever, sore throat, easy bruising, or unusual bleeding. · Avoid alcohol completely while taking this medicine. · You will need regular blood tests to monitor your blood counts and adjust the dose. · Use effective contraception during treatment and for at least 6 months after stopping. Men should also use contraception. · Do not take folic acid supplements unless prescribed, as they may reduce the effect. · If you miss a dose, take it as soon as you remember unless it is almost time for the next dose. Do not double the dose. · Store at room temperature, away from moisture and heat. |