Hydroxycarbamide

Mechanism of action

Ribonucleotide reductase turns ribonucleotides into the deoxyribonucleotides needed to build DNA. Hydroxycarbamide quenches the tyrosyl free radical in the enzyme's small subunit, so deoxynucleotides run out and DNA synthesis stops in S-phase cells, while RNA and protein synthesis continue. It also sensitises cells to radiotherapy. In sickle cell disease it raises fetal haemoglobin (HbF), which dilutes sickle haemoglobin and reduces painful crises.

1. Hydroxycarbamide quenches the tyrosyl radical of ribonucleotide reductase
2. Deoxyribonucleotides run out
3. DNA synthesis stops in S phase
4. In sickle cell disease, fetal haemoglobin rises

Indications

• Sickle cell anaemia: fewer painful crises and transfusions (adults and children). Sickle cell disease →
• Chronic myeloid leukaemia resistant to other treatment. Chronic myeloid leukaemia →
• Myeloproliferative neoplasms such as essential thrombocythaemia and polycythaemia vera, to control high counts. Essential thrombocythaemia and primary myelofibrosis →
• Locally advanced head and neck squamous cell carcinoma, with chemoradiation. Head and neck squamous cell carcinoma (oral cavity and oropharynx, HPV) →

Adverse effects

Common

• Myelosuppression (leukopenia, anaemia, sometimes thrombocytopenia), quickly reversible
• Macrocytosis (large red cells) early in treatment
• Nausea, mouth sores, diarrhoea or constipation
• Skin changes: rash, darkening, nail changes, hair thinning

Contraindications

• Hypersensitivity to hydroxycarbamide or any component

Key interactions

Didanosine and stavudine (antiretrovirals)

Fatal and non-fatal pancreatitis, hepatotoxicity and peripheral neuropathy.

Live vaccines

Risk of severe infection from the vaccine; avoided during treatment.

Radiotherapy

Radiation recall: redness of previously irradiated skin.

What is monitored

• Complete blood count at baseline and regularly during treatment
• Kidney function (dose depends on it)
• Skin, legs and nails at each visit
• In sickle cell disease: fetal haemoglobin and mean cell volume show the response

Administration and safety

• Hazardous drug: capsules are handled with gloves and are not opened; carers wash hands after contact.
• Sun protection is advised because of the risk of skin cancer.

Pregnancy and breastfeeding

Can cause fetal harm; effective contraception is advised for women and men during treatment and for some time after.

Nursing care

• Check counts before each refill; hold and report low neutrophils or platelets.
• Inspect the legs and ankles for ulcers, especially in myeloproliferative disease.
• Teaching: protect from the sun, use effective contraception, and report fever, bleeding or a painful skin sore.
• In sickle cell disease, encourage adherence: the benefit appears only with steady use.

Pharmacokinetics

Absorption

Oral; peak levels within a few hours.

Distribution

Throughout body water; concentrates in white and red blood cells.

Metabolism

Partly by saturable liver metabolism and by urease from gut bacteria.

Elimination

Kidneys; the dose is reduced in renal impairment.

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Connections

← Back to the class: Antimetabolites

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - HYDROXYUREA capsule (DailyMed (U.S. National Library of Medicine), 2026); Hydroxyurea: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.