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All about: Hydroxyurea

Big Image Pronouncation: (high-DROX-ee-you-REE-uh)
Class: Antisickling agent

Trade Names:
Droxia
- Capsules 200 mg
- Capsules 300 mg
- Capsules 400 mg

Trade Names:
Hydrea
- Capsules 500 mg

Gen-Hydroxyurea (Canada)

Mechanism of Action

Pharmacology

Inhibits DNA synthesis, interferes with conversion of ribonucleotides to deoxyribonucleotides, and may inhibit incorporation of thymidine into DNA.

Pharmacokinetics

Absorption

Hydroxyurea is rapidly absorbed. T max is 1 to 4 h, and the bioavailability is 79% to 100%.

Distribution

Hydroxyurea distributes rapidly and widely in the body, concentrates in leukocytes and erythrocytes, readily crosses blood brain barrier, and is secreted in breast milk. Vd is 0.65L/kg.

Metabolism

Up to 50% of oral dose undergoes conversion not fully characterized. In one minor route, hydroxyurea is degraded by urease in intestinal bacteria.

Elimination

Hydroxyurea is excreted by 2 nonlinear pathways, hepatic metabolism and first-order renal excretion. Approximately 40% to 80% is excreted in urine within 12 h. Elimination t ½ is approximately 2.8 to 4.5 h.

Indications and Usage

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.

Unlabeled Uses

Thrombocythemia; HIV; psoriasis; cervical carcinoma; polycythemia vera.

Contraindications

Marked bone marrow suppression; severe anemia; hypersensitivity to product.

Dosage and Administration

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

Sickle Cell Anemia
Adults Initial dose

PO 15 mg/kg/day as a single dose. If blood counts are acceptable levels, dose may be increased by 5 mg/kg/day every 12 wk until max tolerated dose (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 every 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 Intermittent therapy

PO 80 mg/kg (2,000 to 3,000 mg/m 2 ) as a single dose every third day.

Continuous therapy

PO 20 to 30 mg/kg as a single daily dose. Hold the dose if WBC decreases to less than 2,500/mm 3 or platelet count less than 100,000/mm 3 .

Concomitant Irradiation Therapy (Carcinoma of Head and Neck)
Adults

PO 80 mg/kg as a single dose every third day, beginning at least 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.

General Advice

  • Administer without regard to food, but administer in a consistent manner (either with or without food).
  • Administer with food if GI upset occurs.
  • If patient is unable to swallow capsules, the contents of the capsule can be emptied into a glass of water and swallowed immediately.
  • Follow procedures for proper handling and disposal of anticancer drugs.
  • If contents of capsule are spilled, wipe up immediately with a damp disposable towel and discard in a closed container, such as a plastic bag.

Storage/Stability

Store capsules at controlled room temperature (59° to 86°F) in a tightly closed container.

Drug Interactions

Antiretroviral agents (eg, didanosine, indinavir, stavudine)

Hepatotoxicity, fatal hepatic failure, and severe neurotoxicity reported with concomitant use in HIV-positive patients.

Didanosine

Pancreatitis, occasionally resulting in death, reported with concomitant use in HIV-positive patients.

Fluorouracil

Coadministration may cause neurotoxicity.

Uricosuric agents (eg, probenecid)

Hydroxyurea may increase serum uric acid levels.

Laboratory Test Interactions

Serum uric acid, BUN, and creatinine levels may be increased.

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; leukopenia; anemia.

Metabolic

Weight gain.

Renal

Temporary impairment of renal tubular function; uric acid nephropathy.

Respiratory

Pulmonary infiltrates and fibrosis.

Miscellaneous

Fever; parvovirus B-19 infection; chills; malaise.

Precautions

Warnings

Treatment of patients with hydroxyurea capsules may be complicated by severe, sometimes life-threatening adverse reactions. Hydroxyurea is mutagenic, clastogenic, and genotoxic. Secondary leukemias have been reported in patients receiving long-term hydroxyurea for myeloproliferative disorders.


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.

Renal Function

May temporarily impair renal tubular function accompanied by elevated serum uric acid, BUN, and creatinine levels.

Bone marrow function

Because hydroxyurea is cytotoxic and myelosuppressive, do not administer if bone marrow function is markedly depressed. Ensure that hemoglobin, WBC with differential, and platelet counts are determined before starting therapy and at least weekly during therapy.

Carcinogenesis

Hydroxyurea is presumed to be a human carcinogen.

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.

Overdosage

Symptoms

Mucocutaneous toxicity, soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, stomatitis.

Patient Information

  • Review dosing schedule with patient (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 either with or without food but to be consistent. Advise patient to take with food if stomach upset occurs.
  • If patient unable to swallow capsules advise patient that the contents of the capsule can be emptied into a glass of water and swallowed immediately.
  • Advise patient that if a dose is missed, take it as soon as possible. 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 health care provider: fever, chills, or other signs of infection; sore throat, 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 health care provider: epigastric pain, nausea, vomiting, sweating, abdominal tenderness or distension, right upper abdominal pain, yellowing of the skin or eyes, dark urine.
  • Advise patient that medication may cause drowsiness, constipation, redness of the face, skin rash, itching, and hair loss and to notify health care provider if these occur and are bothersome or intolerable.
  • Advise women of childbearing potential to use effective contraception during therapy.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

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