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

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

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

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp: Unlikely to be dialysed. Dose as in normal renal function

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