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Hydroxyurea (Monograph)

Brand names: Droxia, Hydrea
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Warning

    Toxicity

  • Highly toxic drug with a low therapeutic index.c

  • Possible severe, sometimes life-threatening or fatal, adverse effects.177 178

    Limit to Qualified Personnel

  • Administer only under supervision of qualified clinicians experienced in use of cytotoxic therapy.177 178 (See Adequate Patient Evaluation and Monitoring under Cautions.)

    Carcinogenicity

  • Hydroxyurea is genotoxic and is a presumed human carcinogen;177 178 also, mutagenic and clastogenic in vitro.177 178

  • Secondary leukemias have been reported in patients receiving long-term therapy for myeloproliferative disorders (e.g., polycythemia vera, thrombocythemia).177 178

  • Carefully consider risks of developing secondary malignancies against the benefits of therapy.a (See Carcinogenicity under Cautions.)

Introduction

Antineoplastic agent; exhibits beneficial effects against sickle cell anemia; exhibits antiviral activity.100 101 102

Uses for Hydroxyurea

Chronic Myelogenous Leukemia

Treatment of resistant chronic myelogenous leukemia (CML).166 177 212

Used as an alternative agent for the palliative treatment of chronic-phase CML in patients who cannot undergo allogeneic bone marrow or stem cell transplantation;166 167 212 superior to busulfan for the palliative treatment of CML.212 213

Used as an alternative agent for the palliative treatment of the accelerated phase of CML.166 212

Used to reduce WBC count prior to bone marrow transplantation or initiation of interferon alfa therapy.212

Sickle Cell Anemia

Palliative treatment of sickle cell anemia generally in patients with recurrent moderate to severe painful crises occurring on at least 3 occasions during the preceding 12 months (designated an orphan drug by FDA for this use).106 107 111 113 114 116 117 118 122 123 124 125 151 155 156 157 158 178 179

Therapy is prophylactic; the drug has no role in the treatment of a crisis in progress.117

Polycythemia Vera

Management of polycythemia vera† [off-label] including use as an adjunct to intermittent phlebotomy.136 143 144 145 146 152 164 171 174 176

Cervical Cancer

Has been used for treatment of cervical cancer† [off-label];206 207 208 however, other agents are considered more effective.203 204 205 209

Head and Neck Cancer

Has been used in combination with radiation therapy for local control of primary squamous cell (epidermoid) carcinoma of the head and neck, excluding the lip.177

Melanoma

Has been used for treatment of melanoma;177 however, other agents are preferred.166

Ovarian Cancer

Has been used for treatment of recurrent, metastatic, or inoperable ovarian cancer;177 however, other agents are preferred.166

Hydroxyurea Dosage and Administration

General

Chronic Myelogenous Leukemia

Sickle Cell Anemia

Polycythemia Vera

Administration

Administer orally.177 178

If the patient is unable to swallow the commercially available capsules, the contents may be emptied into a glass of water and administered immediately.227

Handle the drug with care; the powder should not be allowed to come in contact with skin or mucous membranes.177 To minimize risk of exposure, wear impervious gloves at all times when handling the drug or bottles containing the drug, including unpacking and inspection, transport within a facility, dose preparation, and dose administration.a b 229 230 Wash hands before and after contact with the drug or bottles containing the drug.229 230 If the contents of the capsule are spilled, wipe the powder immediately with a damp disposable towel and discard in a closed container.177 Caution patients on proper handling, storage, and disposal of the drug.177 229 230

Extemporaneously Compounded Oral Solution

An extemporaneously compounded oral solution of hydroxyurea has been prepared using the commercially available capsules and a flavored syrup.231

Standardize 4 Safety

Standardized concentrations for an extemporaneously prepared oral solution of hydroxyurea have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.252 Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.252 For additional information on S4S (including updates that may be available), see [Web].252

Table 1: Standardize 4 Safety Compounded Oral Liquid Standards for Hydroxyurea252

Concentration Standards

100 mg/mL

Dosage

Adults

Chronic Myelogenous Leukemia
Oral

20–30 mg/kg as a single dose daily.177

Continue therapy indefinitely in patients who show regression or arrest of tumor growth.177

Solid Tumors
Oral

80 mg/kg as a single dose every third day.177 Alternatively, 20–30 mg/kg as a single dose daily.177

Head and Neck Cancer
Oral

80 mg/kg as a single dose every third day.177

Administration should begin at least 7 days before initiation of radiation therapy; continue during irradiation as well as afterward provided patient is closely monitored and no unusual or severe reactions occur.177

Sickle Cell Anemia
Oral

Initially, 15 mg/kg as a single dose.178

Adjust dosage according to patient's blood cell count.178 If blood cell count is in an acceptable range, dosage may be increased in increments of 5 mg/kg daily once every 12 weeks to a maximum tolerated dosage of up to 35 mg/kg daily.178 Dosage should not be increased if blood cell counts are between the acceptable range and the toxic range.178

If blood cell count is in the toxic range, discontinue hydroxyurea until hematologic recovery occurs; treatment may then be resumed at a reduced daily dose.178 (See Hematologic Toxicity under Dosage and Administration.)

Polycythemia Vera† [off-label]
Oral

Initially, 15–20 mg/kg daily.164

Most adults respond adequately to dosages of 500 mg to 1 g daily; some patients may respond to as little as 1.5–2 g weekly (along with occasional phlebotomy), while others may require dosages as high as 1.5–2 g or more daily.164

Dosage Modification for Toxicity
Hematologic Toxicity

In patients receiving hydroxyurea for antineoplastic therapy, withhold therapy when leukocyte count is <2500/mm3 or platelet count is <100,000/mm3.177 Reevaluate leukocyte and platelet counts after 3 days; therapy may be resumed when the counts return to acceptable levels.177 Severe anemia may be managed without interrupting hydroxyurea therapy.177

If hematologic recovery does not occur promptly during combined hydroxyurea and radiation therapy, irradiation may be interrupted.177

In patients receiving hydroxyurea for sickle cell anemia, withhold therapy when neutrophil count is <2000/mm3, the platelet count is <80,000/mm3, the hemoglobin concentration is <4.5 g/dL, or the reticulocyte count is <80,000/mm3 with a hemoglobin concentration of <9 g/dL.178 Following hematologic recovery, resume therapy at a reduced daily dose of 2.5 mg/kg less than the dose that resulted in toxicity.178 Resume titration of the dosage by increasing or decreasing the daily dose in increments of 2.5 mg/kg once every 12 weeks to a maximum tolerated dosage (up to 35 mg/kg daily) at which the patient does not experience hematologic toxicity during 24 consecutive weeks of therapy.178 Further attempts should not be made to titrate to a dosage level that resulted in hematologic toxicity during 2 separate periods of dosage adjustment.178

GI Toxicity

Temporarily discontinue hydroxyurea if severe gastric distress (e.g., nausea, vomiting, anorexia) resulting from combined hydroxyurea and radiation therapy occurs.177

Dermatologic Toxicity

Discontinue hydroxyurea if cutaneous vasculitic toxicity (e.g., vasculitic ulcerations, gangrene) occurs in patients with myeloproliferative disorders; initiate alternative cytoreductive agents as clinically indicated.228 229

Prescribing Limits

Adults

Sickle Cell Anemia
Oral

Maximum 35 mg/kg daily.178

Special Populations

Hepatic Impairment

No specific dosage adjustment recommended, however close monitoring of hematologic parameters is recommended.177 178

Renal Impairment

Dosage reduction may be necessary; close monitoring of hematologic parameters recommended.177 178 a b

Sickle Cell Anemia
Oral

If Clcr ≥60 mL/min, reduce initial dosage to 15 mg/kg daily.a

If Clcr is <60 mL/min, reduce initial dosage to 7.5 mg/kg daily.a

For hemodialysis patients, administer 7.5 mg/kg following dialysis.a

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in renal function; lower dosages may be required.b (See Renal Impairment under Dosage and Administration.)

Detailed Hydroxyurea dosage information

Cautions for Hydroxyurea

Contraindications

Warnings/Precautions

Warnings

Hematologic Effects

Risk of bone marrow depression (manifested commonly as leukopenia and less commonly as thrombocytopenia and anemia);177 178 usually reversible following discontinuance of the drug.116 117 121 178

Do not initiate therapy for neoplasms in patients with myelosuppression (i.e., leukocyte count <2500/mm3, platelet count <100,000/mm3, or severe anemia).177

Do not initiate therapy for sickle cell anemia in patients with myelosuppression (i.e., neutrophil count <2000/mm3, platelet count <80,000/mm3, hemoglobin concentration <4.5 g/dL, or reticulocyte count <80,000/mm3 with a hemoglobin concentration of <9 g/dL).178

Prior Irradiation or Myelosuppressive Therapy

Possible additive myelosuppressive effects; use with caution in patients who have recently received other cytotoxic drugs or radiation therapy.177

Erythrocytic Abnormalities

Possible self-limiting megaloblastic erythropoiesis; resembles pernicious anemia but not related to vitamin B12 or folic acid deficiency.177 b Often occurs soon after initiation of therapy and becomes less pronounced as therapy continues.177 b

Hydroxyurea may delay plasma iron clearance and reduce the rate of iron utilization by the erythrocytes; red blood cell survival time not altered.177

Hydroxyurea-induced macrocytosis may mask incidental folic acid deficiency; prophylactic administration of folic acid recommended.178

Patients with HIV Infection

Potentially fatal pancreatitis and hepatotoxicity and potentially severe peripheral neuropathy reported in patients with HIV infection receiving concomitant therapy with antiretroviral agents.177 178 (See Specific Drugs under Interactions.)

Use of hydroxyurea in combination with antiretroviral agents is not recommended.187 Close monitoring for clinical manifestations of pancreatitis and hepatotoxicity is necessary in patients with HIV infection receiving hydroxyurea, especially when the drug is administered in combination with didanosine and/or stavudine.177 178 Permanently discontinue hydroxyurea if signs and/or symptoms of pancreatitis or hepatotoxicity develop.177 178

Carcinogenicity

Possible leukemia or secondary malignancies; assess risk/benefits of therapy for nonmalignant disease (e.g., sickle cell anemia,116 117 118 119 120 151 152 178 polycythemia vera).116 117 136 143 145 146 152 164 171 172

Skin cancer has been reported in patients receiving long-term therapy.177 178

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals.127 128 129 131 133 134 135 177 178

Use during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective.214 If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.177 178

Cutaneous Vasculitic Toxicity

Potentially severe cutaneous vasculitic toxicities (e.g., vasculitic ulcerations, gangrene) reported in patients with myeloproliferative disorders; reported most often in patients with a history of, or concomitantly receiving, interferon therapy.228 229 230 a b

If cutaneous vasculitic ulcerations occur, discontinue hydroxyurea therapy and initiate alternative cytoreductive therapy as indicated.228 229 a b

General Precautions

Adequate Patient Evaluation and Monitoring

Highly toxic drug with a low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.c Administer only under constant supervision by clinicians experienced in therapy with cytotoxic agents or the use of this agent for sickle cell anemia.177 178

Monitor hematologic status carefully before initiation of therapy and repeatedly during therapy.177 178 Perform blood counts (e.g., hemoglobin, total leukocyte counts, platelet counts, reticulocyte counts) at least weekly during therapy for neoplasms177 and at least every 2 weeks during therapy for sickle cell anemia;178 bone marrow examination also may be necessary.177 178

Evaluate renal and hepatic function before initiation of therapy and check repeatedly during therapy.177 178

Impairment of Fertility

Testicular atrophy, decreased spermatogenesis, and reduced ability to impregnate females were observed in male rats.177 178

Specific Populations

Pregnancy

Category D.

Lactation

Distributed into milk.177 178 Discontinue nursing or the drug.177

Pediatric Use

Safety and efficacy not established.116 117 124 177 178 179

Geriatric Use

Possibility exists of greater sensitivity to the drug in some geriatric individuals.b Select dosage with caution.b (See Geriatric Patients under Dosage and Administration.)

Substantially eliminated by kidneys; assess renal function periodically and select dosage with caution since geriatric patients are more likely to have decreased renal function.229 b

Pharmacokinetics not evaluated in geriatric patients.a b

Hepatic Impairment

Possible decreased elimination; close monitoring of hematologic parameters is recommended.177 178

Renal Impairment

Substantially eliminated by kidneys; increased risk of toxicity.b Use with caution.a b

Possible decreased elimination; reduced dosage and close monitoring of hematologic parameters is recommended.177 178 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Bone marrow suppression.a b

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Antiretroviral agents (didanosine, stavudine)

Potentially fatal pancreatitis and hepatotoxicity reported in patients with HIV infection receiving concomitant therapy177 178

Concomitant use is not recommended;187 if used, close monitoring for clinical manifestations of pancreatitis and hepatotoxicity is necessary177 178

Interferon

Potentially severe cutaneous vasculitic toxicities reported in patients with myeloproliferative disorders with a history of, or concomitantly receiving, interferon therapya b

Discontinue hydroxyurea if cutaneous vasculitic ulcerations occura b (see Cutaneous Vasculitic Toxicity under Cautions)

Myelosuppressive agents

Possible additive bone marrow depression177

Dosage adjustment may be required177

Uricosuric agents

Potential increased serum uric acid concentrations177

Dosage adjustment of uricosuric agent may be required177
Hydroxyurea drug interactions (more detail)

Hydroxyurea Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract.177 178

Peak serum concentrations are attained within 1–4 hours following oral administration.177 178

Food

Effect of food on absorption is not known.177 178

Distribution

Extent

Rapidly distributed throughout the body; concentrates in leukocytes and erythrocytes.177 178 Crosses the blood-brain barrier and is distributed into ascitic fluid.177 178

Hydroxyurea crosses the placenta and is distributed into milk.177 178

Elimination

Metabolism

Up to 50% of an orally administered dose is metabolized in the liver; however, precise metabolic pathways not determined.177 178

Elimination Route

Nonlinear excretion via 2 separate routes: A saturable pathway most likely involving hepatic metabolism, and a linear pathway involving first-order renal excretion.177 178

Special Populations

Renal and/or hepatic impairment may decrease elimination.177 178

Stability

Storage

Oral

Capsules

Tight, light-resistant containers at 25°C.177 178

Store out of reach of children and pets.177

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydroxyurea

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg

Droxia

Bristol-Myers Squibb

250 mg

Hydroxyurea Capsules

300 mg

Droxia

Bristol-Myers Squibb

400 mg

Droxia

Bristol-Myers Squibb

500 mg*

Hydrea

Bristol-Myers Squibb

Hydroxyurea Capsules

AHFS DI Essentials™. © Copyright 2025, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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