hydroxyurea
Droxia, Hydrea

Available forms
Available by prescription only
Capsules: 250 mg, 500 mg
Tablets: 1,000 mg

Indications and dosages
Dosage and indications for hydroxyurea may vary. Check current literature for recommended protocol.
 Solid tumors. Adults: 80 mg/kg P.O. as a single dose q 3 days. Or, 20 to 30 mg/kg P.O. as a single daily dose.
 Head and neck cancers, excluding the lip. Adults: 80 mg/kg P.O. as a single dose q 3 days.
 Resistant chronic myelocytic leukemia. Adults: 20 to 30 mg/kg P.O. as a single daily dose.
 Pain relief for sickle-cell crisis. Adults: 15 mg/kg PO as a single dose, then titrate upward in increments of 5 mg/kg every 12 weeks to a maximum tolerated dose of 35 mg/kg daily.

Pharmacodynamics
Antineoplastic action: The exact mechanism of the cytotoxic action of hydroxyurea is unclear. However, hydroxyurea inhibits DNA synthesis without interfering with RNA or protein synthesis. Drug may act as an antimetabolite, inhibiting the incorporation of thymidine into DNA, and it may also damage DNA directly.

Pharmacokinetics
Absorption: Well absorbed after oral administration. Higher serum levels are achieved if drug is given as a large, single dose rather than in divided doses.
Distribution: Hydroxyurea crosses the blood-brain barrier.
Metabolism: About 50% of an oral dose is degraded in the liver.
Excretion: The remaining 50% is excreted in urine as unchanged drug. The metabolites are excreted through the lungs as carbon dioxide and in urine as urea.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with marked bone marrow depression (leukopenia [less than 2,500 WBCs/mm³], thrombocytopenia [less than 100,000 platelets/mm³], or severe anemia).
  Use cautiously in patients with impaired renal function. Don’t administer to pregnant women or women of childbearing age who may become pregnant unless potential benefit to patient outweighs possible risk to fetus.

Interactions
Drug-drug. Didanosine, indinavir, stavudine: Fatal pancreatitis has occurred when used together. Avoid use together.
Fluorouracil: Neurotoxicity may occur. Avoid use together.

Adverse reactions
CNS: hallucinations, headache, dizziness, disorientation, seizures, fever, malaise.
GI: anorexia, nausea, vomiting, diarrhea, stomatitis, constipation, pancreatitis.
Hematologic: leukopenia, thrombocytopenia, anemia, megaloblastosis, bone marrow suppression with rapid recovery (dose-limiting and dose-related).
Skin: rash, alopecia, erythema.
Other: chills.

Effects on lab test results
• May increase BUN, creatinine, and uric acid levels.
• May decrease hemoglobin, hematocrit, and WBC, RBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, ulceration of buccal and GI mucosa, facial erythema, maculopapular rash, disorientation, hallucinations, and impairment of renal tubular function.
 Treatment is usually supportive and includes transfusion of blood components.

Special considerations
• Dosage may need to be adjusted after other chemotherapy or radiation therapy.
• Auditory and visual hallucinations and blood toxicity increase when decreased renal function exists.
• Avoid all I.M. injections when platelet counts are below 100,000/mm³.
• Store capsules in tight container at room temperature. Avoid exposure to excessive heat.
• Monitor CBC at least weekly throughout therapy.
• Monitor intake and output levels; patient must remain hydrated.
• Drug may exacerbate postirradiation erythema.
Pregnant patients
• Don’t give drug to pregnant women or women of childbearing age who may become pregnant unless potential benefit to patient outweighs possible risk to fetus.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. However, because of risk of serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.
Pediatric patients
• Children may need a lower dosage.
Geriatric patients
• Elderly patients may be more sensitive to effects of drug, requiring a lower dosage.

Patient education
• Emphasize importance of continuing drug therapy despite nausea and vomiting.
• Encourage daily fluid intake of 10 to 12 8-oz glasses to increase urine output and facilitate excretion of uric acid.
• Advise patient of possible adverse reactions, and instruct him to immediately report postdose vomiting, and unusual bruising or bleeding.
• Advise patient to avoid exposure to people with infections and to report signs of infection immediately.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use