No

Antineoplastic Agent, Antimetabolite

CML in chronic phase; radiosensitizing agent in the treatment of primary brain tumors, head and neck tumors, uterine cervix and nonsmall cell lung cancer, psoriasis, sickle cell anemia and other hemoglobinopathies; treatment of hematologic conditions such as essential thrombocythemia, polycythemia vera, hypereosinophilia, and hyperleukocytosis due to acute leukemia. Has shown activity against renal cell cancer, melanoma, ovarian cancer, head and neck cancer, and prostate cancer. Management of sickle cell anemia - to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the preceding 12 months). Has been used in combination with didanosine and other antiretrovirals in the treatment of HIV.

D

Severe anemia, severe bone marrow suppression; WBC <2500/mm³ or platelet count <100,000/mm³; hypersensitivity to hydroxyurea

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Use with caution in patients with renal impairment, in patients who have received prior irradiation therapy, and in the elderly.

>10%:

Central nervous system: Drowsiness

Gastrointestinal: Mild to moderate nausea and vomiting may occur, as well as diarrhea, constipation, mucositis, ulceration of the GI tract, anorexia, and stomatitis

Hematologic: Myelosuppression: Dose-limiting toxicity, causes a rapid drop in leukocyte count (seen in 4-5 days in nonhematologic malignancy and more rapidly in leukemia); thrombocytopenia and anemia occur less often; reversal of WBC count occurs rapidly, but the platelet count may take 7-10 days to recover

WBC: Moderate

Platelets: Moderate

Onset (days): 7

Nadir (days): 10

Recovery (days): 21

1% to 10%:

Dermatologic: Dermatologic changes (hyperpigmentation, erythema of the hands and face, maculopapular rash, or dry skin), alopecia

Hepatic: Abnormal LFTs and hepatitis

Renal: Increased creatinine and BUN due to impairment of renal tubular function

Miscellaneous: Carcinogenic potential

<1%: Neurotoxicity, dizziness, disorientation, hallucination, seizures, headache, fever, facial erythema, hyperuricemia, dysuria, elevated hepatic enzymes, rarely, acute diffuse pulmonary infiltrates; dyspnea, skin cancer

Symptoms of overdose: Myelosuppression, facial swelling, hallucinations, disorientation

Treatment is supportive

Increased effect: Zidovudine, zalcitabine, didanosine: Synergy

Increased toxicity:

Fluorouracil: The potential for neurotoxicity may increase with concomitant administration

Cytarabine: Modulation of its metabolism and cytotoxicity reduction of cytarabine dose is recommended

Store capsules at room temperature; capsules may be opened and emptied into water (will not dissolve completely)

Thought to interfere (unsubstantiated hypothesis) with synthesis of DNA, during the S phase of cell division, without interfering with RNA synthesis; inhibits ribonucleoside diphosphate reductase, preventing conversion of ribonucleotides to deoxyribonucleotides; cell-cycle specific for the S phase and may hold other cells in the G₁ phase of the cell cycle.

Absorption: Readily from the GI tract ( greater than or equal to 80%)

Distribution: Readily crosses the blood-brain barrier; well distributed into intestine, brain, lung, kidney tissues, effusions and ascites; appears in breast milk

Metabolism: In the liver; 50% degradation by enzymes of intestinal bacteria

Half-life: 3-4 hours

Time to peak serum concentration: Within 2 hours

Elimination: Renal excretion of urea (metabolite) and respiratory excretion of CO₂ (metabolic end product); 50% of the drug is excreted unchanged in urine

Oral (refer to individual protocols): All dosage should be based on ideal or actual body weight, whichever is less:

No FDA-approved dosage regimens have been established; dosages of 1500-3000 mg/m² as a single dose in combination with other agents every 4-6 weeks have been used in the treatment of pediatric astrocytoma, medulloblastoma, and primitive neuroectodermal tumors

CML: Initial: 10-20 mg/kg/day once daily; adjust dose according to hematologic response

Adults: Dose should always be titrated to patient response and WBC counts; usual oral doses range from 10-30 mg/kg/day or 500-3000 mg/day; if WBC count falls to <2500 cells/mm³, or the platelet count to <100,000/mm³, therapy should be stopped for at least 3 days and resumed when values rise toward normal

Solid tumors:

Intermittent therapy: 80 mg/kg as a single dose every third day

Continuous therapy: 20-30 mg/kg/day given as a single dose/day

Concomitant therapy with irradiation: 80 mg/kg as a single dose every third day starting at least 7 days before initiation of irradiation

Resistant chronic myelocytic leukemia: 20-30 mg/kg/day divided daily

HIV: 1000-1500 mg daily in a single dose or divided doses

Sickle cell anemia (moderate/severe disease): Initial: 15 mg/kg/day, increased by 5 mg/kg every 12 weeks if blood counts are in an acceptable range until the maximum tolerated dose of 35 mg/kg/day is achieved or the dose that does not produce toxic effects

Acceptable range:

Neutrophils greater than or equal to 2500 cells/mm³

Platelets greater than or equal to 95,000/mm³

Hemoglobin >5.3 g/dL, and

Reticulocytes greater than or equal to 95,000/mm³ if the hemoglobin concentration is <9 g/dL

Toxic range:

Neutrophils <2000 cells/mm³

Platelets <80,000/mm³

Hemoglobin <4.5 g/dL

Reticulocytes <80,000/mm³ if the hemoglobin concentration is <9 g/dL

Monitor for toxicity every 2 weeks; if toxicity occurs, stop treatment until the bone marrow recovers; restart at 2.5 mg/kg/day less than the dose at which toxicity occurs; if no toxicity occurs over the next 12 weeks, then the subsequent dose should be increased by 2.5 mg/kg/day; reduced dosage of hydroxyurea alternating with erythropoietin may decrease myelotoxicity and increase levels of fetal hemoglobin in patients who have not been helped by hydroxyurea alone

Dosing adjustment in renal impairment:

Cl_cr 10-50 mL/minute: Administer 50% of normal dose

Cl_cr <10 mL/minute: Administer 20% of normal dose

Hemodialysis: Supplemental dose is not necessary. Hydroxyurea is a low molecular weight compound with high aqueous solubility that may be freely dialyzable, however, clinical studies confirming this hypothesis have not been performed; peak serum concentrations are reached within 2 hours after oral administration and by 24 hours, the concentration in the serum is zero

CAPD effects: Unknown

CAVH effects: Unknown

CBC with differential, platelets, hemoglobin, renal function and liver function tests, serum uric acid

Drowsiness is common; may rarely cause disorientation and hallucinations

Myelosuppression is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take capsules exactly on schedule directed by prescriber (dosage and timing will be specific to purpose of therapy). Contents of capsule may be emptied into a glass of water and taken immediately. You will require frequent monitoring and blood tests while taking this medication to assess effectiveness and monitor adverse reactions. You will be susceptible to infection; avoid crowds, infected persons, and persons with contagious diseases. You may experience nausea, vomiting, or loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); constipation (increased exercise, fluid, or dietary fiber may help); diarrhea (buttermilk, boiled milk, or yogurt may help); mouth sores (frequent mouth care will help). Report persistent vomiting, diarrhea, constipation, stomach pain, or mouth sores; skin rash, redness, irritation, or sores; painful or difficult urination; increased confusion, depression, hallucinations, lethargy, or seizures; persistent fever or chills, unusual fatigue, white plaques in mouth, vaginal discharge, or unhealed sores; unusual lassitude, weakness, or muscle tremors; easy bruising/bleeding; or blood in vomitus, stool, or urine. People not taking hydroxyurea should not be exposed to it; if powder from capsule is spilled, wipe up with damp, disposable towel immediately, and discard the towel in a closed container, such as a plastic bag. Wash hands thoroughly. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Do not breast-feed.

Capsule (Droxia™): 200 mg, 300 mg, 400 mg

Capsule: 500 mg

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Montaner JS, Zala C, Conway B, et al, "A Pilot Study of Hydroxyurea Among Patients With Advanced Human Immunodeficiency Virus (HIV) Disease Receiving Chronic Didanosine Therapy: Canadian HIV Trials Network Protocol 080," J Infect Dis, 1997, 175(4):801-6.

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