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Hydroxyurea Mechanism Of Action

hydroxyurea mechanism of action

Mechanism of action of hydroxyurea. ... Hydroxyurea is well absorbed after oral administration, converted to a free radical nitroxide in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme.

DESCRIPTION

HYDREA (hydroxyurea capsules, USP) is an antimetabolite available for oral use as capsules containing 500 mg hydroxyurea. Inactive ingredients include citric acid, colorants (D&C Yellow No. 10, FD&C Blue No. 1, FD&C Red No. 40, and D&C Red No. 28), gelatin, lactose, magnesium stearate, sodium phosphate, and titanium dioxide.

Yet Another Mechanism of Action for Hydroxyurea in Sickle Cell Disease?

Adenosine is a purine nucleoside derived primarily from the catabolism of adenine nucleotides, ATP and ADP (Figure). The abundance of adenosine is determined by the action of a number of enzymes (Figure). In the extracellular compartment, the ectonucleotidases, CD39 (ectonucleoside triphosphate diphosphohydrolase 1) and CD73 (ecto-5’-nucleotidase), promote the formation of adenosine. Adenosine is degraded by adenosine deaminase (ADA), which can be present on cell surfaces in a complex with CD26. Adenosine signals through four G-protein coupled receptors, which mediate different actions. Recently, potential roles for adenosine in the pathophysiology of sickle cell disease (SCD) have been identified.

DOSAGE & INDICATIONS

20 to 30 mg/kg orally once daily as a single dose. Continue therapy if a response is observed after 6 weeks of therapy. Interrupt hydroxyurea therapy for white blood cell (WBC) counts less than 2500 cells/mm3 or platelet counts less than 100,000 cells/mm3; re-evaluate after 3 days and resume therapy if these blood counts increase to acceptable levels. Hydroxyurea has been administered as single-agent therapy or as part of combination therapy.

What are the side effects of hydroxyurea-oral?

Known side effects include:

bone marrow suppression (drop in white blood cell, red blood cell and platelet counts),

  • anorexia,
  • nausea,
  • vomiting,
  • diarrhea,
  • constipation,
  • sores in the mouth,
  • skin rash,
  • swelling in the hands, feet, legs and face,
  • changes in skin pigmentation,

What is the dosage for hydroxyurea-oral?

For treating cancer: Dose should be titrated based on individual patient response. Capsules should be swallowed whole. Hydroxyurea capsules should be handled with extreme care and disposed of properly because it causes cell damage.

What Hydroxyurea Is Used For:

Chronic myeloid leukemia

Essential thrombocytosis and polycythemia vera

Head and neck cancer (used with radiation therapy)

Melanoma

Refractory ovarian cancer (ovarian cancer that has not responded or progressed after standard therapy).

Note:  If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How Hydroxyurea Is Given:

Hydroxyurea is a pill, taken by mouth.

Take Hydroxyurea exactly as prescribed.

Hydroxyurea may be dissolved in water.

The amount of Hydroxyurea that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated.  Your doctor will determine your dose and schedule.

Precautions:

Before starting Hydroxyurea treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).  Do not take aspirin, or products containing aspirin unless your doctor specifically permits this.Do not receive any kind of immunization or vaccination without your doctor's approval while taking Hydroxyurea.Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (Hydroxyurea may be hazardous to the fetus.  Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).

For both men and women: Do not conceive a child (get pregnant) while taking Hydroxyurea. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.

People who are not taking Hydroxyurea should not be exposed to it.  If powder from a capsule spills, it should be wiped with a damp disposable towel, placed in a plastic bag, and discarded.  Hands should be washed thoroughly.

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