Hydroxyurea (hydroxyurea)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Hydroxyurea is an antimetabolite antineoplastic agent and exhibits beneficial effects against sickle cell anemia.
The exact mechanism of antineoplastic activity of hydroxyurea has not been fully determined. Some studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting like a ribonucleotide reductase inhibitor without interfering with the synthesis of RNA or protein.
The mechanisms by which hydroxyurea exert its beneficial effects in patients with sickle cell anemia are unclear; however, known pharmacologic effects that may contribute to its beneficial effects include increasing fetal hemoglobin (HbF) levels in RBCs, decreasing neutrophils, increasing the water content of RBCs, increasing the deformability of RBCs, and altering the adhesion of RBCs to endothelium.
Hydroxyurea is readily absorbed from the GI tract. Hydroxyurea oral bioavailability is 85-100%. Peak serum concentrations are attained within 1-4 hours following oral administration of hydroxyurea capsules and tablets.
Following administration of hydroxyurea oral solution, peak serum concentrations occur within 0-2 hours. Disproportionate increases in peak plasma concentrations and AUCs result when drug dosage is increased. The effect of food on the absorption of hydroxyurea has not been determined.
Hydroxyurea distributes throughout the body and concentrates in leukocytes and erythrocytes. Hydroxyurea distributes into milk. Up to 60% of an orally administered dose of hydroxyurea is metabolized in the liver or undergoes degradation by urease found in intestinal bacteria.
Mean cumulative urinary excretion of approximately 40% of the administered dose was reported in patients with sickle cell anemia. The elimination half-life of hydroxyurea is 2-4 hours.
The pharmacokinetics of hydroxyurea tablets are similar between children 4-17 years of age and adults. Model estimated steady state exposure (AUC) in pediatric patients receiving a daily dosage of 15 mg/kg of hydroxyurea oral solution is lower in patients 6 months to <2 years and 2 to <6 years of age by 40 and 28%, respectively, compared to adults at the same dosage (Xromi(R) not approved for use in adults). Following administration of hydroxyurea oral solution, exposure to hydroxyurea is similar between patients 6 to <18 years of age and adults.
USES: This medication is used by people with sickle cell anemia to reduce the number of painful crises caused by the disease and to reduce the need for blood transfusions. Some brands are also used to treat certain types of cancer (such as chronic myelogenous leukemia, squamous cell carcinomas).
Generic name: hydroxyurea
Pronunciation: (hi-DROX-ee-you-REE-uh)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Hydroxyurea
Indications
The following indications are listed for Hydroxyurea:
- Chronic Myelocytic Leukemia
- Squamous Cell Carcinoma Of Head And Neck
Also known as: Chronic Granulocytic Leukemia, Chronic Leukemic Myelosis, Chronic Myelogenic Leukemia, Chronic Myelogenous Leukemia, Chronic Myeloid Leukemia, Epidermoid Carcinoma Of The Head And Neck.
Dosing
Dosage of hydroxyurea should be based on actual or ideal body weight, whichever is less.
Hydroxyurea is administered orally. The effect of food on the absorption of hydroxyurea is not known. While hydroxyurea can be taken without regard to meals, an attempt should be made to standardize the time of administration each day.
Hydroxyurea is available as oral capsules (Droxia(R), Hydrea(R)), oral solution (Xromi(R)), and film-coated tablets (Siklos(R)).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Formal studies evaluating potential drug interactions with hydroxyurea have not been performed to date.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to hydroxyurea or any component of the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported with hydroxyurea capsules in at least 30% of adult patients with sickle cell anemia include hematological, GI symptoms, and anorexia.
Adverse effects reported in more than 10% of patients receiving hydroxyurea tablets include infections and neutropenia in pediatric patients and infections, headache, and dry skin in adults.
Adverse effects reported in more than 5% of pediatric patients with sickle cell anemia receiving hydroxyurea oral solution include neutropenia, thrombocytopenia, and papular rash.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of hydroxyurea tablets (Siklos(R)) have been established in pediatric patients 2-18 years of age with sickle cell anemia and recurrent moderate to severe painful crises. Use of hydroxyurea tablets in this age group is supported by data from a cohort study of 405 pediatric patients aged 2 to <18 years; of the 405 pediatric patients, 274 were 2-11 years of age and 108 pediatric patients were 12-16 years of age. Pediatric patients 2-16 years of age had a higher incidence of neutropenia compared to older patients.
Safety and efficacy of hydroxyurea oral solution (Xromi(R)) have been established in pediatric patients 6 months of age and older with sickle cell anemia and recurrent moderate to severe painful crises. Use of Xromi(R) in this age group is based on a pharmacokinetic, efficacy, and safety study in which 32 pediatric patients 6 months to <18 years of age were enrolled.
Safety and efficacy of hydroxyurea capsules (Droxia(R) and Hydrea(R)) have not been established in pediatric patients.
The pharmacokinetics of hydroxyurea are similar in pediatric patients 4-17 years of age and adults.
Continuous follow-up of growth is recommended in pediatric patients who receive hydroxyurea.
Based on animal studies and the drug's mechanism of action, hydroxyurea can cause fetal harm when administered to pregnant women. Hydroxyurea crosses the placenta and has been shown to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys, when administered in doses within onefold of the human dose based on body surface area. Administration of 180 mg/kg daily (about 0.8 times the maximum recommended human daily dosage on a mg/m2 basis) or 30 mg/kg daily (about 0.3 times the maximum recommended human daily dosage on a mg/m2 basis) of the drug resulted in fetal malformations (including partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae) in rats or rabbits, respectively. Embryotoxicity, manifested as decreased fetal viability, reduced live litter sizes, and developmental delays, also was observed. Single doses of >=375 mg/kg (approximately 1.7 times the maximum recommended human daily dosage on a mg/m2 basis) in rats resulted in growth retardation and impaired learning ability.
In a retrospective analysis of a cohort of 123 adult patients treated with hydroxyurea, 61% of 23 reported pregnancies had no adverse developmental outcomes. In other cases with known evaluation, pregnancy had been interrupted voluntarily or upon medical advice.
Postmarketing data from 3 reported pregnancies when the father was being treated and 16 pregnancies when 15 mothers were being treated with hydroxyurea show that out of 13 cases with known evolution, 5 pregnancies had no adverse developmental outcomes, 4 led to preterm birth, and 4 were terminated early. Verify pregnancy status before initiating hydroxyurea.
Hydroxyurea is distributed into human milk. Because of the potential for serious adverse reactions to hydroxyurea (including carcinogenicity) in nursing infants, avoid breast-feeding during treatment with hydroxyurea.
Because geriatric patients may be particularly sensitive to the effects of hydroxyurea, they may require a lower dosage of the drug. Geriatric patients also may be more likely to have renal impairment and are therefore at greater risk of adverse reactions; dosage should be carefully selected and renal function monitoring may be helpful in such patients.
Because geriatric patients may be particularly sensitive to the effects of hydroxyurea, they may require a lower dosage of the drug.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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