What is hydroxyurea used for?

From the Guidelines

Hydroxyurea is primarily used to treat sickle cell disease, certain types of cancer, and polycythemia vera, with its most significant benefit being the reduction of morbidity and mortality in patients with sickle cell disease by increasing fetal hemoglobin production and reducing painful crises 1.

Key Uses of Hydroxyurea

• Sickle cell disease: Hydroxyurea increases fetal hemoglobin production, which prevents red blood cells from sickling and reduces painful crises.
• Certain types of cancer: Hydroxyurea inhibits DNA synthesis in rapidly dividing cells, making it effective in treating cancers such as chronic myeloid leukemia, head and neck cancer, and cervical cancer.
• Polycythemia vera: Hydroxyurea helps control excessive red blood cell production.

Administration and Monitoring

• The typical adult dose ranges from 15-35 mg/kg/day taken orally, with adjustments based on blood counts 1.
• Patients should maintain adequate hydration while taking hydroxyurea and inform healthcare providers about all medications they're taking to avoid interactions.
• Regular blood count monitoring is required due to the risk of bone marrow suppression.

Side Effects and Precautions

• Common side effects include bone marrow suppression, gastrointestinal issues, and skin changes 1.
• Long-term use requires monitoring for potential secondary malignancies, though the overall benefit typically outweighs this risk for indicated conditions.
• Hydroxyurea is contraindicated in patients with marked bone marrow depression, including leukopenia, thrombocytopenia, or anemia 1.

Recent Guidelines and Recommendations

• The 2014 National Heart, Lung, and Blood Institute guidelines recommend offering hydroxyurea to every child with HbSS or Sb0-thalassemia at 9 months of age, even without clinical symptoms 1.
• The European LeukemiaNet recommends hydroxyurea as a first-line treatment for high-risk patients with polycythemia vera and essential thrombocythemia 1.

From the FDA Drug Label

Hydroxyurea capsules are indicated for the treatment of: • Resistant chronic myeloid leukemia. • Locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation.

Hydroxyurea is used for the treatment of resistant chronic myeloid leukemia and locally advanced squamous cell carcinomas of the head and neck (in combination with chemoradiation) 2. The main uses of hydroxyurea are:

• Resistant chronic myeloid leukemia
• Locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation 2 2.

From the Research

Uses of Hydroxyurea

• Hydroxyurea is used as a cancer chemotherapeutic agent, specifically in the treatment of myeloproliferative disorders such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis 3.
• It is also used in combination therapy for the management of malignant melanoma, head and neck cancers, and brain tumors 3.
• Hydroxyurea is used to treat chronic myelogenous leukemia, and has been shown to be a preferable agent to busulfan due to its lower toxicity 4.
• In addition to its use in cancer treatment, hydroxyurea is used to treat sickle cell disease, where it has been shown to reduce the frequency of painful episodes and increase the level of fetal hemoglobin 5.
• Hydroxyurea has also been investigated as a potential treatment for other conditions, including Alzheimer's disease, where it has been shown to have a promising effect on preventing cognitive decline 6.

Mechanism of Action

• Hydroxyurea acts by inhibiting the enzyme ribonucleoside diphosphate reductase, which is necessary for DNA synthesis 3, 6.
• This inhibition leads to a decrease in the production of deoxyribonucleotides, which are necessary for DNA replication and cell division 3.
• As a result, hydroxyurea is able to arrest cells in the S-phase of the cell cycle, leading to a decrease in cell proliferation 6.

Side Effects

• Hydroxyurea can cause a number of side effects, including gastrointestinal disturbance, bone marrow depression, and infertility 3, 5.
• Prolonged treatment or higher doses of hydroxyurea can also lead to cell death due to accumulation of DNA damage and oxidative stress 6.
• There is also a potential risk of carcinogenesis or leukemogenic risk associated with long-term use of hydroxyurea, as evidenced by a case report of a patient with sickle cell disease who developed acute myeloid leukemia after 26 months of treatment with hydroxyurea 7.