HYDREA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDREA (HYDREA).
Hydroxyurea inhibits ribonucleotide reductase, thereby reducing the conversion of ribonucleotides to deoxyribonucleotides, which impairs DNA synthesis and leads to cell cycle arrest in S phase. It also induces fetal hemoglobin (HbF) production by increasing nitric oxide and soluble guanylyl cyclase activity.
| Metabolism | Hydroxyurea is metabolized via hepatic and extrahepatic pathways, including metabolism by the liver and possibly by red blood cells. The exact enzymes involved are not fully characterized. |
| Excretion | Renal excretion is the primary route of elimination, with 50-80% of an administered dose recovered as unchanged drug in urine within 24 hours. Biliary/fecal excretion accounts for less than 10%. |
| Half-life | The terminal elimination half-life is approximately 3-4 hours in patients with normal renal function. In patients with creatinine clearance <60 mL/min, half-life may be prolonged up to 8-12 hours, necessitating dose adjustment. |
| Protein binding | Hydroxyurea is rapidly absorbed and exhibits negligible protein binding (<10%) to serum albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.5 L/kg, indicating distribution into total body water. Higher Vd may be seen in patients with ascites or edema. |
| Bioavailability | Oral bioavailability is 80-100% (mean ~90%). Absorption is rapid with peak plasma concentrations occurring 1-2 hours after oral administration. |
| Onset of Action | Oral administration: Reduction in elevated white blood cell count in chronic myeloid leukemia begins within 24-48 hours. For essential thrombocythemia, platelet count reduction starts within 3-5 days. Clinical benefits in sickle cell disease (e.g., decreased crisis rate) may be evident after 4-8 weeks of therapy. |
| Duration of Action | Duration of hematologic effect (suppression of blood counts) persists for about 24-48 hours after a single dose. Continuous dosing maintains effect. Myelosuppression resolves within 10-14 days after discontinuation. |
| Action Class | Anticancer-others |
| Brand Substitutes | Hydrogem 500mg Capsule, Hydrox 500mg Capsule, Readrox 500mg Capsule, Hydran 500mg Capsule, Ondrea 500mg Capsule |
20-30 mg/kg orally once daily; typical adult dose 500 mg to 1.5 g daily. Maximum dose 2 g per day.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 50-80 mL/min: reduce dose by 50%; CrCl 10-50 mL/min: reduce dose by 50% and extend interval; CrCl <10 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B and C: reduce dose by 50%; caution with Child-Pugh C due to increased toxicity. |
| Pediatric use | 20-30 mg/kg orally once daily (max 2 g); adjust for renal function if applicable. |
| Geriatric use | Start at lower end of dosing range (500 mg daily) and titrate based on renal function and tolerance; monitor for myelosuppression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYDREA (HYDREA).
| Breastfeeding | Hydroxyurea is excreted into human milk. The M/P ratio is unknown. Potential serious adverse effects in the nursing infant include myelosuppression and carcinogenesis. Breastfeeding is not recommended during therapy and for at least 7 days after last dose. |
| Teratogenic Risk | Hydroxyurea is teratogenic in animal studies. In humans, first trimester exposure is associated with major congenital malformations including craniofacial, skeletal, and cardiac defects. Second and third trimester exposure risks include intrauterine growth restriction, low birth weight, and neonatal myelosuppression. Use is contraindicated in pregnancy due to teratogenicity. |
■ FDA Black Box Warning
Hydroxyurea is carcinogenic and can cause secondary malignancies such as leukemia and skin cancer. It is also myelosuppressive and can cause severe bone marrow suppression, requiring close monitoring of blood counts.
| Serious Effects |
["Severe bone marrow suppression (e.g., severe anemia, leukopenia, thrombocytopenia)","Pregnancy (Category D)","Lactation (discontinue nursing or drug)","Hypersensitivity to hydroxyurea"]
| Precautions | ["Myelosuppression (anemia, leukopenia, thrombocytopenia); monitor complete blood counts weekly during therapy.","Risk of secondary malignancies (acute leukemia, skin cancer); avoid long-term use if possible.","Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.","Impaired renal function; dose adjustment required for CrCl <60 mL/min.","Contraindicated in pregnancy; advise effective contraception.","May cause macrocytosis, which can mask response to vitamin B12 or folate deficiency; consider supplementation.","Increased risk of pancreatitis and hepatotoxicity, especially with high doses."] |
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| Fetal Monitoring | If exposed inadvertently during pregnancy, perform detailed fetal anatomy ultrasound in the second trimester. Serial growth ultrasounds should be considered due to risk of intrauterine growth restriction. Complete blood count with differential should be monitored monthly in pregnant women on hydroxyurea. |
| Fertility Effects | Hydroxyurea may cause oligospermia or azoospermia in males and ovarian failure in females, potentially impairing fertility. Effects are likely reversible upon discontinuation, but data are limited. |