CLINICAL USE

Antineoplastic agent

DOSE IN NORMAL RENAL FUNCTION

IV: 1.4–1.5 mg/m2 weekly; maximum 2 mg Consult relevant local protocol

PHARMACOKINETICS

  • Molecular weight                           : 923
  • %Protein binding                           : 75
  • %Excreted unchanged in urine     :
  • 10 to 20     :
  • Volume of distribution (L/kg)       : 5–11
  • half-life – normal/ESRD (hrs)      : 15–155/Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Dose as in normal renal function
  • <10           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                : Unlikely to be dialysed. Dose as in normal renal function
  • HD                     : Unlikely to be dialysed. Dose as in normal renal function
  • HDF/high flux   : Unknown dialysability. Dose as in normal renal function
  • CAV/VVHD      : Unlikely to be dialysed. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Anti-epileptics: phenytoin levels may be reduced
  • Antifungals: metabolism possibly inhibited by itraconazole and posaconazole (increased risk of neurotoxicity)
  • Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis)

    ADMINISTRATION

    Reconstition

    –

    Route

    IV

    Rate of Administration

    Slow bolus

    Comments

    May be administered into fast running drip of sodium chloride 0.9% or glucose 5%

    OTHER INFORMATION

    Most of an IV dose is excreted into the bile after rapid tissue binding Metabolised by cytochrome P450 (in the CYP 3A subfamily). Elimination is primarily biliary; excreted into bile and faeces (67% within 72 hours, 40–50% as metabolites), 10% excreted in urine in 24 hrs

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