Hydroxyurea (Hydrea) — Clinical FAQs

Question 1

What is Hydroxyurea FDA-approved to treat?

Accepted Answer

Hydroxyurea is FDA-approved for the following oncology indications: 1. Chronic myelogenous leukemia (CML) — cytoreductive therapy; largely supplanted by BCR-ABL tyrosine kinase inhibitors for definitive treatment but retained for acute leukocytosis/leukostasis management and as a bridging agent 2. Resistant chronic myelocytic leukemia (Hydrea) 3. Locally advanced squamous cell carcinoma of the head and neck — in combination with radiation therapy (Hydrea) 4. Recurrent, metastatic, or inoperable ovarian carcinoma (Hydrea) 5. Sickle cell anemia — prevention of painful vaso-occlusive crises in adults with recurrent moderate-to-severe episodes (Droxia; FDA approved 1998); separately approved in pediatric patients ≥2 years.

Question 2

How does Hydroxyurea work (mechanism of action)?

Accepted Answer

Hydroxyurea is a specific inhibitor of ribonucleotide reductase (RNR), the enzyme catalyzing the rate-limiting step of de novo deoxyribonucleotide synthesis — the reduction of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. By chelating the tyrosyl free radical in the RRM2 subunit of RNR, hydroxyurea depletes the intracellular dNTP pool, blocking DNA synthesis and arresting cells at the G1/S interface. This S-phase specificity enables rapid cytoreduction of actively proliferating cells including leukemic blasts and hyperproliferative hematopoietic precursors. In sickle cell disease, hydroxyurea additionally stimulates fetal hemoglobin (HbF) production through mechanisms involving nitric oxide signaling and stress erythropoiesis, diluting sickle hemoglobin (HbS), reducing red cell sickling, and decreasing vaso-occlusive crisis frequency.

Question 3

How is Hydroxyurea administered?

Accepted Answer

Hydroxyurea is administered Oral (PO). Hydrea capsules: 500 mg.

Question 4

What are the most common side effects of Hydroxyurea?

Accepted Answer

The most commonly reported side effects of Hydroxyurea (≥10% incidence) include: Myelosuppression — leukopenia (most common dose-limiting toxicity), anemia, thrombocytopenia, Nausea and vomiting (mild to moderate), Diarrhea, Mucositis / oral ulcers, Skin hyperpigmentation (palmar, plantar; common with prolonged use) and others (11 total). Consult your oncologist for complete prescribing information.

Question 5

Does Hydroxyurea have a black box warning?

Accepted Answer

Yes. Hydroxyurea carries FDA black box warning(s) regarding: 1. Myelosuppression: hydroxyurea causes severe myelosuppression including leukopenia, anemia, and thrombocytopenia. CBC with differential must be monitored before initiation and throughout therapy. Interrupt therapy for severe bone marrow depression; resume when counts recover. 2. Secondary malignancies: long-term hydroxyurea use is associated with the development of secondary leukemia (AML) and myelodysplastic syndromes, particularly in patients treated for myeloproliferative neoplasms. Monitor for secondary malignancies throughout the course of therapy.

Question 6

Is Hydroxyurea safe during pregnancy?

Accepted Answer

Hydroxyurea pregnancy safety: Category D — causes fetal harm. Hydroxyurea is a potent teratogen and mutagen in animals, causing skeletal and visceral malformations at doses well below the human therapeutic range. Effective contraception is required during therapy and for at least 6 months after the last dose in females; males should use contraception during and for at least 1 year after therapy. Breastfeeding is contraindicated.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Hydroxyurea — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms