Hydroxyurea

A to Z Drug Facts

Actions Inhibits DNA synthesis, interferes with conversion of ribonucleotides to deoxyribonucleotides, and may inhibit incorporation of thymidine into DNA. Hydroxyurea is readily absorbed from the GI tract, reaching peak serum concentrations within » 1 to 2 hr. About 50% of an oral dose is degraded in the liver and excreted into the urine as urea and as respiratory carbon dioxide; the remainder is excreted intact in the urine.

 Indications Reduce frequency of painful crises and need for blood transfusion in adults with sickle cell anemia with recurrent moderate-to-severe painful crises; treatment of melanoma; resistant chronic myelocytic leukemia (CML); recurrent, metastatic, or inoperable carcinoma of ovary; as an adjunct to irradiation in local control of primary squamous cell carcinomas of head and neck, excluding lip.

Thrombocythemia; HIV; psoriasis; cervical carcinoma; sickle cell disease; polycythemia vera.

 Contraindications Marked bone marrow suppression; severe anemia.

 Route/Dosage Base dosage on patient's actual or ideal weight, whichever is less.

Sickle Cell Anemia

ADULTS: PO Initial dose 15 mg/kg/day as a single dose. If blood counts are acceptable levels, dose may be increased by 5 mg/kg/day q 12 wk until max tolerated dose (ie, highest dose not producing toxic blood counts over 24 consecutive wk), or 35 mg/kg/day is reached.

Dose is not increased if blood counts are between acceptable and toxic levels. If blood counts are considered toxic, discontinue hydroxyurea until hematologic recovery, then resume therapy after reducing dose by 2.5 mg/kg/day from dose associated with hematologic toxicity. Then, titrate dose up or down q 12 wk in 2.5 mg/kg/day increments until patient is at a stable dose that does not result in hematologic toxicity for 24 wk. Any dose that produces hematologic toxicity twice should not be given again.

Solid Tumors

ADULTS: PO Intermittent therapy: 80 mg/kg (2000 to 3000 mg/m²) as a single dose every third day; Continuous therapy: 20 to 30 mg/kg as a single daily dose. Hold the dose for WBC < 2500/mm³ or platelet count < 100,000/mm³.

Concomitant Irradiation Therapy (Carcinoma of Head and Neck)

ADULTS: PO 80 mg/kg as a single dose every third day, beginning ³ 7 days before initiation of irradiation and continue during radiotherapy and indefinitely afterwards, provided patient is adequately observed and exhibits no unusual or severe reactions.

Resistant CML

ADULTS: PO Continuous therapy of 20 to 30 mg/kg as a single daily dose.

Interactions

Fluoruracil

Coadministration may cause neurotoxicity.

Lab Test Interferences None well documented.

 Adverse Reactions

DERMATOLOGIC: Hair loss; skin rash; black-pigmented nails; maculopapular rash, skin ulcers, dermatomyositis-like changes, peripheral and facial erythema; hyperpigmentation; skin and nail atrophy; scaling and violet papules; skin cancer. GI: Stomatitis; anorexia; nausea; vomiting; diarrhea; constipation; increased LFTs. HEMATOLOGIC: Neutropenia; low reticulocyte and platelet levels; bleeding; bone marrow suppression. METABOLIC: Weight gain. RESPIRATORY: Pulmonary infiltrates and fibrosis. RENAL: Temporary impairment of renal tubular function; uric acid nephropathy. OTHER: Fever; parvovirus B-19 infection; chills; malaise.

 Precautions

Pregnancy: Category D. Lactation: Excreted in breast milk. Children: Safety and efficacy not established. Elderly: May be more sensitive to the effects of hydroxyurea and may require a lower dosage regimen. Bone marrow function: Because hydroxyurea is cytotoxic and myelosuppressive, do not administer if bone marrow function is markedly depressed. Erythema: Patients who have received prior irradiation therapy may have an exacerbation of postirradiation erythema. Erythrocytic abnormalities: Self-limiting megaloblastic erythropoiesis is often seen early in hydroxyurea therapy. Renal toxicity: May temporarily impair renal tubular function accompanied by elevated serum uric acid, BUN, and creatinine levels. Carcinogenesis: Hydroxyurea is presumed to be a human carcinogen.

 Administration/Storage

• Administer prescribed number of capsules once daily or every third day without regard to food, but administer in a consistent manner (ie, with or without food).
• Do not administer if WBC < 2500/mm³ or platelet count < 100,000/mm³.
• Do not administer if signs or symptoms of pancreatitis or hepatitis are noted.
• If contents of capsule are spilled, wipe up immediately with a damp disposable towel and discard in a closed container, such as plastic bag.
• Store capsules at controlled room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note history of bone marrow depression and renal or hepatic impairment.
• Ensure that hemoglobin, WBC, and platelet counts are determined before starting therapy and at least weekly during therapy.
• Ensure that baseline LFT's and kidney function are determined before starting therapy and periodically during therapy.
• Monitor HIV-infected patient for signs and symptoms of pancreatitis (eg, epigastric pain, nausea, vomiting, sweating, abdominal tenderness, distension) and hepatotoxicity (eg, right upper quadrant pain, jaundice, dark urine), and report to health care provider if noted.
• Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops.
• Monitor patient for GI, CNS, and general body side effects. Report to health care provider if noted and significant.

 Patient/Family Education

• Explain name, dose, action, and potential side effects of drug.
• Review dosing schedule with patient (ie, every day or every third day).
• Advise patient that dose is individualized based upon condition being treated and size of the patient.
• Advise patient to take each dose with or without food, but to be consistent.
• Extra fluid intake is recommended.
• Advise patient that if a dose is missed, take it as soon as possible, but if close to the next dose, do not double the dose to catch up, and take the next dose as scheduled.
• Advise patient to immediately report any of the following to the health care provider: fever, chills or other signs of infection, sore throat, diarrhea, nausea, vomiting or appetite loss, sores in the mouth or on the lips, unusual bruising or bleeding, skin rash.
• Advise HIV-infected patient to report any of the following to the health care provider: epigastric pain, nausea, vomiting, sweating, abdominal tenderness or distension, right upper abdominal pain, yellowing of the skin or eyes, dark urine.
• Instruct women to notify their health care provider if planning on becoming pregnant or are breastfeeding. Contraceptive measures are recommended.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
• Instruct patient to not take any prescription or otc medications or dietary supplements unless advised to do so by the health care provider.
• Advise patient that follow-up examinations and lab tests will be required to monitor therapy and to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts