BLACK BOX WARNING
- myelosuppression
- teratogenicity
- secondary leukemias
hydroxyurea
Brand: Hydrea, Droxia
⚠ BBW ISMP High Alert Prototype Drug
Drug Class: antimetabolite antineoplastic
Drug Family: antineoplastic
Subclass: ribonucleotide reductase inhibitor
Organ Systems: hematology-oncology
Mechanism of Action
Inhibits ribonucleotide reductase, blocking conversion of ribonucleotides to deoxyribonucleotides; depletes the dNTP pool required for DNA synthesis; S-phase specific. In sickle cell disease, increases fetal hemoglobin (HbF) production by an incompletely understood mechanism involving epigenetic HBG gene activation.
ribonucleotide reductase (RNR)
Indications
- chronic myeloid leukemia (CML) — cytoreduction, now largely replaced by TKIs
- polycythemia vera
- essential thrombocythemia
- sickle cell disease (reduces painful crises and acute chest syndrome)
- head and neck cancer (with radiation as radiosensitizer)
Contraindications
- hydroxyurea hypersensitivity
- severe bone marrow suppression
- pregnancy (teratogenic)
Adverse Effects
Common
- myelosuppression (dose-dependent)
- skin changes (leg ulcers, melanonychia, dermatomyositis-like skin findings)
- mucositis
Serious
- severe myelosuppression
- secondary leukemia (with long-term use)
- teratogenicity
- leg ulcers (can be refractory and require drug discontinuation)
Pharmacokinetics (ADME)
| Absorption | well-absorbed orally (~80%) |
| Distribution | widely distributed; crosses BBB |
| Metabolism | partial hepatic |
| Excretion | renal (50% as unchanged drug; 50% as urea metabolite) |
| Half-life | 3–4 hours |
| Onset | hours |
| Peak | 1–4 hours |
| Duration | 24 hours |
| Protein Binding | minimal |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| didanosine/stavudine (HIV NRTIs) | additive risk of pancreatitis and peripheral neuropathy via mitochondrial toxicity | major |
| antiretrovirals generally | hydroxyurea inhibits RNR, increasing intracellular activation of certain NRTIs; has been used to enhance ddI activity but increases toxicity | moderate |
Nursing Considerations
- Handle hydroxyurea as a cytotoxic agent; wear gloves when handling capsules.
- Monitor CBC weekly initially, then every 2 weeks; dose should be held if WBC <2500/mm3 or platelets <100,000/mm3.
- For sickle cell disease, hydroxyurea requires dose optimization over several months; baseline labs include HbF level, CBC, reticulocyte count.
- Assess skin regularly for leg ulcers — a unique adverse effect; discontinue if ulcers develop.
Clinical Pearls
- Hydroxyurea is the only FDA-approved medication for sickle cell disease that reduces painful crises by increasing fetal hemoglobin (HbF) production; HbF inhibits HbS polymerization, reducing sickling — the mechanism of HbF induction is partially via nitric oxide and involves epigenetic regulation of the gamma-globin gene.
- In sickle cell disease, therapeutic response is monitored by measuring HbF percentage; target HbF >20% is associated with clinical benefit (fewer vaso-occlusive crises).
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.