Hydroxyurea

  • Usually 1-2g/day in divided doses
  • Minimal protein binding = 100% bioavailable
  • Pregnancy Category D

  • Metabolism incompletely understood (but Acetohydroxamic acid; important metabolite)
  • 80% renally excreted

  • Inhibition of ribonucleotide diphosphate reductase leading to impaired DNA (deoxyribonucleic acid) synthesis & DNA strand breakage & cellular death
  • Radiation sensitizer (prevents cells from repairing damage)
  • Alters gene expression via hypomethylation

Note

  • Most effective in proliferating cells during S phase when DNA is being synthesized “cell cycle specific”
  • Concentrate within leukocytes

Food & drug administration

  • Melanoma (metastatic & gastrointestinal)
  • Chronic lymphocytic leukemia (treatment-resistant)
  • Ovarian carcinomas
  • Squamous cell carcinoma of head and neck; except lip (concomitantly with radiation)

Off label

  • Sweets syndrome
  • Erythromelalgia
  • Hypereosinophilic syndrome 
  • Psoriasis (3rd line)

Absolute

  • Hypersensitivity
  • Pregnancy
  • Lactation

Relative

  • Cardiopulmonary disease 
  • Hepatic disease
  • Renal disease 

Hematologic disorders (chronic anemia)

  • Active infection

Hematologic 

  • Myelosuppression #1
  • Macrocytic changes with anemia 

Gastrointestinal 

  • Dyspepsia (may be taken with food or antacids to minimize) 

Genitourinary 

  • Renal (increased creatinine/blood urea nitrogen, hematuria, proteinuria) 

Infectious 

  • Opportunistic with myelosuppression 

Cutaneous 

  • Reversible alopecia
  • Hyperpigmentation of skin/nails
  • Leg ulcerations
  • Dermatomyositis-like eruption
  • Lichenoid drug reactions
  • Photosensitivity
  • Radiation recall

  • Other myelosuppresive agents
  • Cytarabine

Baseline

  • History & physical exam
  • Complete blood count, chemistry profile, Liver function tests, Urinalysis, tuberculin skin test (if indicated), pregnancy test

FU

  • Complete blood count qweekly x1 month, monthly x3 months, then every 3months
  • Chemistry profile, Liver function tests, Urinalysis, monthly until stable then every 3-6months
  • Discontinue if hemoglobin decreases by 3g/dL, white blood count <4000 or platelets <100,000