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

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Route

Oral

Rate of Administration

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Comments

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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

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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