hydroxycarbamide

CLINICAL USE

Antineoplastic agent

DOSE IN NORMAL RENAL FUNCTION

15–40 mg/kg dailyConsult local protocol

PHARMACOKINETICS

  • Molecular weight                           :76.05
  • %Protein binding                           :75–80
  • %Excreted unchanged in urine     : 9–95
  • Volume of distribution (L/kg)       :0.5
  • half-life – normal/ESRD (hrs)      :2–6/–

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    > 60 85% of normal dose and titrate to response45–60 80% of normal dose and titrate to response30–45 75% of normal dose and titrate to response10–30 50% of normal dose and titrate to response< 10 20% of normal dose and titrate to response

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Likely dialysability. Dose as in GFR <10 mL/min
  • HD                     :Likely dialysability. Dose as in GFR <10 mL/min
  • HDF/high flux   :Likely dialysability. Dose as in GFR <10 mL/min
  • CAV/VVHD      :Likely dialysability. Dose as in GFR=10–30 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis
  • Antivirals: increased toxicity with didanosine and stavudine – avoid concomitant use

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

    OTHER INFORMATION

    Full blood count, renal and hepatic function should be monitored repeatedly during treatmentDosage should be based on the patient’s actual or ideal weight, whichever is lessHydroxyurea has been associated with impairment of renal tubular function and accompanied by elevation in serum uric acid, BUN, and creatinine levelsThe following formula can be used to determine the fraction of normal dose used for renally impaired patients: Fraction of normal dose = (normal dose) × {[f (kf – 1)] + 1}. f = fraction of the original dose excreted as active or toxic moiety (f = 0.35 for hydroxyurea); kf = patient’s creatinine clearance (mL/min) divided by 120 mL/minuteAdminister with caution to patients with marked renal dysfunction; such patients may rapidly develop visual and auditory hallucinations and significant haematologic toxicityAfter oral administration, hydroxyurea is readily absorbed from the GI tract and peak plasma concentrations are reached within 2 hrs. 50% is hepatically metabolised; 50% of a dose recovered in urine within 12 hours, mainly as intact drug; remainder excreted as carbon dioxide via the lungs or via the urine as urea

  • Related News