[.
]
Action/Kinetics:
Inhibits DNA synthesis but not synthesis of RNA or protein. As an antimetabolite, it interferes with the conversion of ribonucleotides to deoxyribonucleotides due to blockade of the ribonucleotide reductase system. May also inhibit incorporation of thymidine into DNA. Effectiveness in sickle cell anemia may be due to increases in hemoglobin F levels in RBCs, decrease in neutrophils, increases in the water content of RBCs, increases the deformability of sickled cells, and altered adhesion of RBCs to the endothelium. Rapidly absorbed from GI tract.
Peak serum concentration: 1-2 hr.
t
1/2: 3-4 hr. Crosses the blood-brain barrier. Degraded in liver; 80% excreted through the urine with 50% unchanged; also excreted as respiratory CO
2.
Uses:
Chronic, resistant, myelocytic leukemia. Carcinoma of the ovary (recurrent, inoperable, or metastatic). Melanoma. With irradiation to treat primary squamous cell carcinoma of the head and neck (but not the lip). Sickle cell anemia (Droxia).
Investigational: Thrombocytopenia, HIV, psoriasis.
Contraindications:
Leukocyte count less than 2,500/mm
3 or thrombocyte count less than 100,000/mm
3. Severe anemia.
Special Concerns:
Use during pregnancy only if benefits clearly outweigh risks. Give with caution to clients with marked renal dysfunction. Geriatric clients may be more sensitive to the effects of hydroxyurea necessitating a lower dose. Dosage has not been established in children.
Additional Side Effects:
Erythrocyte abnormalities including megaloblastic erythropoiesis. Constipation, redness of the face, maculopapular rash.
Laboratory Test Alterations:
Serum uric acid, BUN, and creatinine.
How Supplied:
Capsule: 200 mg, 300 mg, 400 mg, 500 mg
Dosage
?Capsules
Solid tumors, intermittent therapy or when used together with irradiation.
Dose individualized. Usual: 80 mg/kg as a single dose every third day. Intermittent dosage offers advantage of reduced toxicity. If effective, maintain client on drug indefinitely unless toxic effects preclude such a regimen.
Solid tumors, continuous therapy.
20-30 mg/kg/day as a single dose.
Resistant chronic myelocytic leukemia.
20-30 mg/kg/day in a single dose or two divided daily doses.
Concomitant therapy with irradiation for carinoma of the head and neck.
80 mg/kg as a single dose every third day.
Sickle cell anemia.
Initial: 15 mg once daily. Base dosage on the smaller of ideal or actual body weight. Increase dose gradually to the maximum tolerated dose or to 35 mg/kg/day.
