Hydroxyurea

Hydroxyurea is an antineoplastic (anti-cancer) agent used to treat melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and primary squamous cell (epidermoid) carcinomas of the head and neck.

• Hydroxyurea is available under the following different brand names: Droxia, Hydrea, and hydroxycarbamide.

Dosage Forms and Strengths

Capsules

• 200 mg
• 300 mg
• 400 mg
• 500 mg

Dosage Considerations – Should be Given as Follows:

Solid Tumors

• Intermittent Therapy: 80 mg/kg orally every 3 days, OR
• Continuous Therapy: 20-30 mg/kg orally once/day

Head and Neck Tumors

Concomitant therapy with irradiation

• 80 mg/kg orally every 3 days
• Begin 7 days prior to initiation of irradiation

Head and Neck Tumors

• 80 mg/kg orally every 3 days
• Begin 7 days prior to initiation of irradiation

Chronic Myelocytic Leukemia, Resistant

• Continuous Therapy: 20-30 mg/kg orally once/day

Sickle Cell Disease

• Start: 15 mg/kg/day as a single dose; monitor patient's blood count every two weeks
• Titrate by 5 mg/kg/day every 12 weeks
• The dose is not increased if blood counts are between the acceptable range and toxic
• Not to exceed 35 mg/kg/day
• Discontinue therapy until hematologic recovery if blood counts are considered toxic; may resume treatment after reducing the dose by 2.5 mg/kg/day from dose associated with hematological toxicity

Thrombocythemia, Essential (Off-label)

• 15 mg/kg orally once/day
• Titrate to control platelets and maintain white blood cell (WBC) count

HIV, Adjunct Treatment (Off-label)

• 500 mg orally twice daily
• Use with antiretrovirals

Psoriasis (Off-label)

• 1000-1500 mg/day orally once or twice daily

Other Information

• Monitor: complete blood counts (CBC)

Side effects of hydroxyurea include:

• Nausea
• Vomiting
• Constipation
• Diarrhea
• Mucositis
• Acute pulmonary reactions (rare)
• Genetic mutation (long-term use)
• Secondary leukemia (long-term use)
• Elevated BUN, Cr
• Excess uric acid in the blood (hyperuricemia)
• Renal failure
• Rash
• Darkened patches of skin (hyperpigmentation)
• Skin ulcer
• Gangrenous disorder
• Upset stomach
• Skin changes such as peeling or discoloration
• Flu-like symptoms
• Hair loss
• Headache
• Dizziness
• Drowsiness
• Weight gain

Serious side effects of hydroxyurea include:

• Anemia
• Myelosuppression
• Leukemia

Postmarketing side effects of hydroxyurea reported include:

• Tumor lysis syndrome
• Gastric irritation
• Platelet depression

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe interactions of hydroxyurea include:
  • adenovirus types 4 and 7 live, oral
  • anthrax vaccine
  • BCG intravesical live
  • BCG vaccine live
  • didanosine
  • influenza virus vaccine quadrivalent, intranasal
  • measles mumps and rubella vaccine, live
  • measles, mumps, rubella and varicella vaccine, live
  • poliovirus vaccine live oral trivalent
  • rotavirus oral vaccine, live
  • smallpox (vaccinia) vaccine, live
  • typhoid vaccine live
  • varicella virus vaccine live
  • yellow fever vaccine
  • zoster vaccine live
• Serious interactions of hydroxyurea include:
  • human papillomavirus vaccine, bivalent
  • human papillomavirus vaccine, nonavalent
  • human papillomavirus vaccine, quadrivalent
  • tofacitinib
• Hydroxyurea has moderate interactions with at least 115 different drugs.
• Hydroxyurea has no known mild interactions with other drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

• Hydroxyurea therapy may be complicated by severe, sometimes life-threatening, adverse effects; because of this, it should be administered under the supervision of a physician experienced in the use of this medication
• Hydroxyurea is mutagenic and clastogenic, and causes cellular transformation to a tumorigenic phenotype, and is thus unequivocally genotoxic and a presumed transspecies carcinogen that implies a carcinogenic risk to humans; advise sun protection and monitor patients for malignancies
• Hydroxyurea may cause severe myelosuppression; do not administer if bone marrow function is markedly depressed; monitor blood counts at baseline and throughout treatment; interrupt treatment and reduce the dose as necessary
• In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemias have been reported
• It is unknown whether this leukemogenic effect is secondary to hydroxyurea or is associated with the patients' underlying disease
• The physician and patient must very carefully consider the potential benefits relative to the undefined risk of developing secondary malignancies
• This medication contains hydroxyurea
• Do not take Droxia, Hydrea, or hydroxycarbamide if you are allergic to hydroxyurea or any ingredients contained in this drug

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Severe anemia, bone marrow depression
• White blood cell count less than 2500/mm³, platelets less than 100,000/mm³
• Pregnancy, lactation

Effects of Drug Abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Hydroxyurea?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Hydroxyurea?"

Cautions

• Caution in renal impairment, coadministration with myelosuppressive agents.
• Low white blood cell counts (leukopenia and neutropenia) commonly occur; low platelet counts (thrombocytopenia) and anemia are less common; hematologic toxicity is reversible.
• Do not change dose too frequently.
• Not recommended in sickle cell anemia if neutrophils less than 2,000/mm³, platelets less than 80,000/mm³, hemoglobin less than 4 g/dL, or reticulocytes less than 80,000/mm³ when hemoglobin less than 9 g/dL.
• Increased risk of hepatotoxicity, which may be fatal, may occur, particularly in combination with didanosine and stavudine.
• Risk of cutaneous vasculitic toxicities in patients with myeloproliferative disorders, especially with a history of or concurrent interferon therapy.
• Discontinue if white blood cell count is less than 2500/mm³ and/or platelets less than 100,000/mm³.
• Erythrocyte abnormalities were reported; self-limiting megaloblastic erythropoiesis was reported early in treatment, unrelated to vitamin B12 or folic acid deficiency.
• Hyperuricemia may occur; adequate hydration, dosage adjustment, or the initiation of uricosuric agents may be necessary.
• Interferes with analytical analyses of the enzymes (urease, uricase, and lactate dehydrogenase) used in the determination of urea, uric acid, and lactic acid, rendering falsely elevated results.
• Advise females of reproductive potential to use effective contraception during and after treatment for at least 6 months after therapy; advise males of reproductive potential to use effective contraception during and after treatment for at least 1 year after therapy.
• Avoid the use of live vaccine; concomitant use with a live virus vaccine may potentiate the replication of the virus and/or may increase the adverse reaction of the vaccine because normal defense mechanisms may be suppressed; may result in severe infection; antibody response to the vaccine may be decreased.

Pregnancy and Lactation

• Use hydroxyurea during pregnancy only in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk. Advise females of reproductive potential to use effective contraception during and after treatment with hydroxyurea for at least 6 months after therapy; advise males of reproductive potential to use effective contraception during and after treatment for at least 1 year after therapy.
• Hydroxyurea is excreted in breast milk, do not nurse.