hydroxyurea

Hydroxyurea is a chemotherapy drug used to treat some types of cancers including solid tumors, head and neck cancers and chronic myelocytic leukemia, a type of blood cancer. Hydroxyurea is also used to improve symptoms and manage recurrent crises in sickle cell disease. Hydroxyurea is an antimetabolite antineoplastic drug that prevents cancer cell growth and division by interfering with the normal metabolic process within cells.

Hydroxyurea stops the growth and proliferation of cancer cells by preventing DNA synthesis without interfering with the synthesis of RNA or protein. Hydroxyurea prevents DNA synthesis by inhibiting ribonucleotide reductase, an enzyme that is vital for the synthesis phase (S phase) of cell cycle during which the DNA is replicated. Hydroxyurea is also used to enhance the effects of radiation and other types of chemotherapy drugs because it prevents DNA repair.

In sickle cell anemia, hydroxyurea increases the levels of fetal hemoglobin (HbF) in red blood cells (RBCs), which has higher affinity for oxygen. Hemoglobin F is the major type of hemoglobin in the fetus, which drops to about 80% in newborns and less than 1% in normal adults. Hydroxyurea also increases the water content in RBCs, improves the ability of sickle cells to change shape and pass through even tiny blood vessels, and alters their adhesion to the blood vessel walls.

Hydroxyurea is used in the treatment of conditions that include:

• Solid tumors
• Head and neck tumors
• Resistant chronic myelocytic leukemia
• Sickle cell disease

Off-label uses include:

• Essential thrombocythemia, a disorder that produces too many platelets
• Adjunct treatment of human immunodeficiency virus (HIV) infection
• Psoriasis

• Do not use hydroxyurea in patients with previous hypersensitivity to hydroxyurea or any of its components
• Hydroxyurea causes severe bone marrow suppression (myelosuppression); treatment should not be initiated in patients who have significantly depressed bone marrow function; monitor blood count and titrate dose or interrupt treatment if necessary
• Hydroxyurea is carcinogenic; can cause secondary leukemia; monitor the patient
• Long-term therapy can cause skin cancer; monitor for development of secondary malignancies
• Can cause fetal harm; test for pregnancy before initiating treatment; advise patients to use contraception during and for six months to a year after therapy
• Can cause inflammation and tissue damage of blood vessel walls near the skin (cutaneous vasculitic toxicity) and associated ulcers, particularly in patients who are receiving or have received interferon therapy
• Avoid live vaccinations; may result in severe adverse effects and infection because hydroxyurea can lower immune function
• Can lead to pancreatitis, liver toxicity and peripheral neuropathy with concurrent use of antiretroviral drugs in HIV patients
• Can cause RBCs that are larger than normal (macrocytosis)

Common side effects of hydroxyurea include:

• Infections
• Viral infections
• Bacterial infections
• Gastrointestinal disorders
• Low count of neutrophil immune cells (neutropenia)
• Low platelet levels (thrombocytopenia)
• Fever
• Headache
• Vitamin D deficiency
• Anemia

Less common side effects of hydroxyurea include:

• Parvovirus B19 infections
• Skin reactions
• Skin and subcutaneous tissue disorders including:
  • Rash
  • Skin ulcer
  • Excessive skin pigmentation (hyperpigmentation)
  • Darkening of nails (melanonychia)
  • Dryness and atrophy of skin and nails
  • Reddish-violet rash (violet erythema)
  • Lupus erythematosus
• Nervous system disorder that include:
  • Dizziness
  • Drowsiness
  • Hallucinations
  • Disorientation
  • Convulsions
• Renal and urinary disorders
• Respiratory disorders including
  • Cough
  • Shortness of breath (dyspnea)
  • Diffuse pulmonary infiltrates
  • Pulmonary fibrosis
  • Interstitial lung disease
  • Lung inflammations (pneumonitis, alveolitis)
• Metabolic and nutrition disorders
• Loss of appetite (anorexia)
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Inflammation of oral and gastrointestinal mucous lining (mucositis)
• Gastrointestinal ulcers
• Sore mouth (stomatitis)
• Weight gain
• Low magnesium levels in blood (hypomagnesemia)
• Fever
• Chills
• Feeling unwell (malaise)
• Swelling (edema)
• Weakness (asthenia)
• Myelosuppression with conditions that include:
  • Low count of immature (reticulocytes) red blood cells (reticulocytopenia)
  • Abnormally large blood cells (macrocytosis)
  • Anemia from rapid destruction of RBCs (hemolytic anemia)
• Elevated blood urea nitrogen (BUN) and creatinine
• Elevated uric acid levels in blood (hyperuricemia)
• Kidney failure
• Elevation of liver enzymes
• Tissue death (gangrene)
• Low sperm count (oligospermia)
• Lack of sperm production (azoospermia)
• Absence of menstruation (amenorrhea)
• Drug-induced fever

Rare side effects of hydroxyurea include:

• Acute pulmonary reaction
• Genetic mutation (with long-term use)
• Secondary leukemia (with long-term use)

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Capsule

• 200 mg (Droxia)
• 300 mg (Droxia)
• 400 mg (Droxia)
• 500 mg (Hydrea, generic)

Tablet

• 100 mg (Siklos)
• 1000 mg (tripled-scored) (Siklos)

Adult:

Solid Tumors

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

Head and Neck Tumors

Concomitant therapy with irradiation

• 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 every day

Sickle Cell Disease

Hydrea or generic (off-label)

• Start: 15 mg/kg/day as single dose; monitor patient’s blood cell count every 2 weeks  
• Titrate by 5 mg/kg/day every 12 weeks
• Dose is not increased if blood counts are between 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 dose by 2.5 mg/kg/day from dose associated with hematological toxicity

Siklos

• Indicated to reduce frequency of painful crises and the need for blood transfusions in adults with sickle cell anemia who have recurrent moderate-to-severe painful crises
• Initial dose: 15 mg/kg orally every day
• Calculate rounded doses to the nearest 50-mg or 100-mg strength based on clinical judgment
• Monitor blood cell counts every 2 weeks
• Dose adjustment based on blood counts
  • Increase dose 5 mg/kg/day every 8 weeks or if a painful crisis occurs
  • Give until mild myelosuppression (absolute neutrophil count [ANC] 2,000-4,000/mcL) achieved, not to exceed 35 mg/kg/day
  • Increase dosing only if blood counts are in an acceptable range or if a painful crisis occurs
  • Do not increase if myelosuppression occurs

Thrombocythemia, Essential (Off-label)

• 15 mg/kg orally every day
• Titrate to control platelets and maintain WBC count

HIV, Adjunct Treatment (Off-label)

• 500 mg orally twice a day
• Use with antiretrovirals

Psoriasis (Off-label)

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

Pediatric:

Sickle Cell Disease

Siklos

Indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in 2 years or older children with sickle cell anemia with recurrent moderate-to-severe painful crises

Children younger than 2 years: Safety and efficacy not established

2-18 years

Initial dose

• 20 mg/kg orally every day
• Monitor blood counts every 2 weeks

Dose adjustment based on blood counts

• Increase dose 5 mg/kg/day evert 8 weeks or if a painful crisis occurs; give until mild myelosuppression (absolute neutrophil count [ANC] 2,000/mcL to 4,000/mcL) is achieved, not to exceed 35 mg/kg/day
• Increase dosing only if blood counts are in an acceptable range (see Dosage Modifications) or if a painful crisis occurs
• Do not increase if myelosuppression occurs

Dosage Modifications

Hepatic impairment

• Closely monitor hematologic parameters

Renal Impairment

• CrCl 60 mL/min or more: No dosage adjustment is necessary
• CrCl less than 60 mL/min or end-stage renal disease (ESRD):
  • Adult: Reduce dose to 7.5 mg/kg/day and closely monitor the hematologic parameters
  • Pediatric: Reduce dose to 10 mg/kg/day and closely monitor the hematologic parameters
• ESRD patients on dialysis: On dialysis days, administer dose following hemodialysis

Hematologic toxicities

Blood counts acceptable range

• Neutrophils 2,000 cells/mm3 or higher
• Platelets 80,000/mm3 or higher
• Hemoglobin more than 5.3 g/dL
• Reticulocytes 80,000/mm3 or higher if hemoglobin is less than 9 g/dL

Blood counts toxic range

• Neutrophils less than 2,000 cells/mm3
• Platelets less than 80,000/mm3 if hemoglobin is less than 4.5 g/dL
• Reticulocytes less than 80,000/mm3 if hemoglobin is less than 9 g/dL
• Pediatric patients with lower baseline counts may safely tolerate ANC down to 1,250/mm³
• Discontinue treatment until hematologic recovery

Dosing after hematologic recovery

• Reduce dose by 5 mg/kg/day from the dose associated with hematologic toxicity
• May titrate up or down every 8 weeks in 5 mg/kg/day increments
• Patient should be at a stable dose with no hematologic toxicity for 24 weeks
• Permanently discontinue treatment if hematologic toxicity develops twice

Dosing Considerations

• Use fetal hemoglobin (HbF) levels to evaluate the efficacy in clinical use
• Obtain HbF levels every three to four months; monitor for an increase in HbF of at least two-fold over the baseline value
• Verify the pregnancy status of females of reproductive potential before initiating

• Hydroxyurea overdose is toxic to the skin and mucous membranes and can cause symptoms that include oral inflammation (stomatitis), soreness, swelling and scaling of hands and feet, reddish-violet rash (violet erythema), and hyperpigmentation.
• Treatment of hydroxyurea overdose consists of stomach wash (gastric lavage), followed by symptomatic treatment and control of bone marrow function. In case of overdose, seek medical help immediately or contact Poison Control.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of hydroxyurea include:
  • abrocitinib
  • baricitinib
  • BCG products including intravesical
  • cladribine
  • Dengue tetravalent vaccine
  • live vaccines
  • natalizumab
  • poliovirus vaccine live oral trivalent
  • tacrolimus
  • tofacitinib
  • typhoid vaccine
  • upadacitinib
  • yellow fever vaccine
• Serious interactions of hydroxyurea include:
  • coccidioides immitis skin test
  • COVID-19 adenovirus vector and mRNA vaccines
  • deferipone
  • denosumab
  • Influenza virus vaccine quadrivalent, intranasal
  • leflunomide
  • lenograstim
  • lipegfilgrastim
  • palifermin
  • rabies vaccine
  • sipuleucel-T
  • Inactivated vaccines
• Hydroxyurea has moderate interactions with at least 115 different drugs.
• Hydroxyurea has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Animal tests show that hydroxyurea can cause fetal harm; there are no well-controlled studies on use of hydroxyurea in pregnant women.
• Hydroxyurea should be used during pregnancy only in life-threatening emergencies, when no safer treatment is available.
• Females of reproductive potential should use contraception during and for 6 months following therapy.
• Males with female partners of reproductive potential should use contraception during and for at least a year after treatment.
• If pregnancy occurs during hydroxyurea therapy, the patient should be informed of potential risks to the fetus.
• Hydroxyurea is present in breast milk; either nursing or the drug should be discontinued, taking into account the importance of the drug to the mother and potential fetal risks.

• Take hydroxyurea exactly as prescribed
• Handle hydroxyurea with care; minimize exposure to individuals not on hydroxyurea therapy; use disposable gloves while handling
• Wash your hands before and after handling the bottle or capsules
• Keep safely out of reach of children and pets
• There is a risk for secondary malignancies including leukemia and skin cancer; protect yourself from sun exposure
• Check with your doctor before taking any vaccinations, particularly live vaccines