• Basic Info
• Top Questions
• Clinical Info
• Interactions

Uses

Chronic Myelogenous Leukemia

Treatment of resistant chronic myelogenous leukemia (CML).

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; superior to busulfan for the palliative treatment of CML.

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

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

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).

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

Polycythemia Vera

Management of polycythemia vera† including use as an adjunct to intermittent phlebotomy.

Cervical Cancer

Has been used for treatment of cervical cancer†; however, other agents are considered more effective.

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.

Melanoma

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

Ovarian Cancer

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

Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.
• Individualize dosage according to actual or ideal body weight, whichever is less.
• Consult published protocols for the dosage of hydroxyurea and other chemotherapeutic agents and the method and sequence of administration.

Chronic Myelogenous Leukemia

• An adequate trial period for determining the antineoplastic effectiveness is 6 weeks.

Sickle Cell Anemia

• Following initiation of therapy, monitor patient's blood cell count every 2 weeks and adjust dosage accordingly. (See Dosage under Dosage and Administration.)
• Some clinicians perform less frequent monitoring (e.g., weekly until stabilization occurs and then every 2 weeks for the initial months of therapy, followed by monthly or less frequent monitoring once response has been established) when the drug is used chronically and dosage is titrated carefully for sickle cell anemia.

Polycythemia Vera

• Individualize dosage according to hematocrit response (usually to less than 45–50%) and hematologic tolerance of the patient.
• Supplemental phlebotomy can be performed as necessary to control hematocrit.

Administration

Administer orally.

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

Handle the drug with care; the powder should not be allowed to come in contact with skin or mucous membranes. To minimize risk of exposure, wear disposable gloves when handling the drug or bottles containing the drug. If the contents of the capsule are spilled, wipe the powder immediately with a damp disposable towel and discard in a closed container.

Dosage

Adults

Chronic Myelogenous Leukemia

Oral

20–30 mg/kg as a single dose daily.

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

Solid Tumors

Oral

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

Head and Neck Cancer

Oral

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

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.

Sickle Cell Anemia

Oral

Initially, 15 mg/kg as a single dose.

Adjust dosage according to patient's blood cell count. 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. Dosage should not be increased if blood cell counts are between the acceptable range and the toxic range.

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. (See Hematologic Toxicity under Dosage and Administration.)

Polycythemia Vera

Oral

Initially, 15–20 mg/kg daily.†

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.†

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. Reevaluate leukocyte and platelet counts after 3 days; therapy may be resumed when the counts return to acceptable levels. Severe anemia may be managed without interrupting hydroxyurea therapy.

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

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. Following hematologic recovery, resume therapy at a reduced daily dose of 2.5 mg/kg less than the dose that resulted in toxicity. 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. Further attempts should not be made to titrate to a dosage level that resulted in hematologic toxicity during 2 separate periods of dosage adjustment.

GI Toxicity

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

Prescribing Limits

Adults

Sickle Cell Anemia

Oral

Maximum 35 mg/kg daily.

Special Populations

Dosage in Hepatic Impairment

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

Dosage in Renal Impairment

Dosage reduction may be necessary; close monitoring of hematologic parameters recommended.

Sickle Cell Anemia

Oral

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

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

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

Geriatric Patients

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