CLINICAL USE

Treatment of advanced breast cancer (where other anthracyclines have failed) Non-small cell lung cancer

DOSE IN NORMAL RENAL FUNCTION

Oral: 60–80 mg/m2 once weekly for 3 weeks IV: 25–30 mg/m2 once a week Maximum 60 mg per dose

PHARMACOKINETICS

  • Molecular weight                           : 1079.1 (as tartrate)
  • %Protein binding                           : 13.5 (78% bound to platelets)
  • %Excreted unchanged in urine     : 18.5
  • Volume of distribution (L/kg)       : >40
  • half-life – normal/ESRD (hrs)      : 28–44

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

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

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis)

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral, IV bolus, infusion

    Rate of Administration

    Bolus: 5–10 minutes Infusion: 20–30 minutes

    Comments

    Dilute bolus in

  • 20 to 50     : mL with sodium chloride 0.9% Dilute infusion in 125 mL with sodium chloride 0.9% Stable for 24 hours at 2–8°C

    OTHER INFORMATION

    Widely distributed in the body, mostly in spleen, liver, kidneys, lungs, thymus; moderately in heart, muscles; minimally in fat, brain, bone marrow. High levels are found in both normal and malignant lung tissues, with slow diffusion out of tumour tissue Metabolism appears to be hepatic. Excretion is mainly by the biliary route (18.5% appears in the urine) Flush line with saline after infusion Dose-limiting toxicity is mainly neutropenia In patients where >75% of the liver volume has been replaced by metastases, it is empirically suggested that the dose be reduced by a third, with close haematological follow-up .

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