Cytoreductive agent / Sickle cell disease / CML Pregnancy: May be a potent mutagenic/genotoxic agent; animal studies show increased congenital defects. Should not be used during pregnancy unless the woman's clinical condition requires it; hydroxycarbamide crosses the placenta. Women of childbearing potential should use effective contraception during treatment and for 6 months after; men should use effective contraception and not father a child during treatment and for 3 months after. Breast-feeding: excreted in human milk — decide whether to discontinue nursing or the drug given potential for serious adverse reactions in nursing infants.

Hydroxycarbamide (Hydroxyurea)

Brand names: Siklos, Xromi, Hydrea

Hydroxycarbamide (hydroxyurea) is an oral antimetabolite cytoreductive agent used in myeloproliferative neoplasms such as polycythaemia vera and essential thrombocythaemia, in chronic myeloid leukaemia, and to reduce vaso-occlusive crises in sickle cell disease.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Chronic myeloid leukaemia (CML): usual initial dose 40 mg/kg daily, dependent on the white cell count; reduced by 50% (20 mg/kg daily) when the white cell count drops below 20 x 10^9/l, then adjusted individually to keep the white cell count at 5-10 x 10^9/l

Route: Oral (capsules swallowed whole, not allowed to disintegrate in the mouth)

Frequency: Daily

Therapy should only be conducted by a physician experienced in oncology or haematology. Doses are based on real or ideal bodyweight, whichever is the less. CML: reduce dose if white cell counts fall below 5 x 10^9/l and increase if counts above 10 x 10^9/l are observed; interrupt therapy if white cell count falls below 2.5 x 10^9/l or platelet count below 100 x 10^9/l until counts rise significantly towards normal. An adequate trial period for antineoplastic effect is six weeks. Other indications: essential thrombocythaemia — usually 15 mg/kg/day, adjusted to maintain platelet count below 600 x 10^9/l without lowering white blood cells below 4 x 10^9/l; polycythaemia vera — start at 15-20 mg/kg/day, adjusted to maintain haematocrit below 45% and platelet count below 400 x 10^9/l (most patients controlled on average daily doses of 500 to 1,000 mg given continuously). Elderly: may be more sensitive and may require a lower dose regimen. No dose recommendation can be given for impaired renal and/or liver function (no data).

Paediatric dose

Route: Oral

Because of the rarity of these conditions in children, dose regimens have not been established (per the UK SPC). No paediatric per-kg dose is stated in this source; verify against a children's formulary.

Dose adjustments

Renal

No data available; a dose recommendation cannot be given for patients with impaired renal (and/or liver) function — special care should be taken, especially at the start of therapy.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients (discontinue if hypersensitivity occurs)
Severe bone marrow depression: leukocytopenia (below 2.5 x 10^9 leukocytes/l), thrombocytopenia (below 100 x 10^9 platelets/l) or severe anaemia

Side effects

Bone marrow depression (dose-limiting) — leukocytopenia, anaemia, thrombocytopenia; decreased CD4 lymphocytes
Anorexia; nausea, vomiting, diarrhoea, constipation, stomatitis, mucositis, abdominal pain (gastrointestinal effects common)
Skin ulcers (especially leg ulcers), cutaneous vasculitis, pruritus, alopecia, maculopapular rash, skin hyperpigmentation, nail disorders
Skin cancer (squamous cell, basal cell) with long-term use
Dysuria and transient renal tubular dysfunction with increased blood uric acid, urea and creatinine; azoospermia, oligospermia; drug fever, asthenia, chills, malaise

Interactions

Antiretroviral agents, in particular didanosine plus stavudine (fatal and non-fatal pancreatitis, hepatotoxicity and severe peripheral neuropathy reported in HIV-infected patients receiving hydroxycarbamide in combination)
Prior or concomitant interferon (increased risk of cutaneous vasculitic toxicities)

Clinical monograph

How it works

It inhibits ribonucleotide reductase, depleting deoxynucleotides and arresting DNA synthesis; in sickle cell disease it also raises fetal haemoglobin, reducing red-cell sickling.

Prescribing in practice

Myelosuppression is dose-limiting and necessitates regular full blood count monitoring with dose adjustment for cytopenias.
It is teratogenic, so effective contraception is required during and for a period after treatment in both men and women of reproductive potential.
Cutaneous reactions including leg ulcers and rarely secondary malignancy can occur with long-term use, warranting periodic skin review.

Monitoring

Monitor full blood count regularly, together with renal and hepatic function, adjusting the dose to maintain counts within target while avoiding excessive myelosuppression.

Counselling the patient

Attend for your regular blood tests so the dose can be kept safe.
Report any unusual bruising, bleeding, fever, mouth ulcers or new skin ulcers promptly.
Use reliable contraception and tell your team if you plan a pregnancy.

Evidence & guidelines

Hydroxycarbamide is established for sickle cell disease following the landmark MSH trial and is recommended by NICE and national guidelines for myeloproliferative neoplasms.

Reference: NICE NG143 Sickle Cell Disease; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways