dosage adjustment of Carboplatin in renal failure




Carboplatin.JPG

Carboplatin

CLINICAL USE

Antineoplastic agent:
  • Ovarian carcinoma of epithelial origin
  • Small cell carcinoma of the lung

    DOSE IN NORMAL RENAL FUNCTION

    Dose = Target AUC × [GFR (mL/min) + 25]where AUC is commonly 5 or 6 depending on protocol used (Calvert equation)

    PHARMACOKINETICS

  • Molecular weight                           :371.2
  • %Protein binding                           :29–89
  • %Excreted unchanged in urine     : 32–70
  • Volume of distribution (L/kg)       :0.23–0.28
  • half-life – normal/ESRD (hrs)      :1.5–6/ Increased

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function. See ‘Other Information’
  • 10 to 20     : Dose as in normal renal function. See ‘Other Information’
  • <10           : Dose as in normal renal function. See ‘Other Information’

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unknown dialysability. Dose as in GFR <10 mL/min
  • HD                     :Dialysed. Dose as in GFR
  • <10           : mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR
  • <10           : mL/min
  • CAV/VVHD      :Unknown dialysability. Dose as in GFR 10 to 20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Aminoglycosides: increased risk of nephrotoxicity and possibly ototoxicity with aminoglycosides, capreomycin, polymyxins or vancomycin
  • Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis

    ADMINISTRATION

    Reconstition

    Route

    IV

    Rate of Administration

    IV infusion

    over 15–60 minutes

    Comments

  • Therapy should not be repeated until 4 weeks after the previous carboplatin course
  • May be diluted with glucose 5%, or sodium chloride 0.9% to concentrations as low as 0.5 mg/mL

    OTHER INFORMATION

  • Patients with abnormal kidney function or receiving concomitant therapy with nephrotoxic drugs are likely to experience more severe and prolonged myelotoxicity
  • Blood counts and renal function should be monitored closely
  • Some units still use a dose in normal renal function of 400 mg/m2. In this instance, the dose should be reduced to 50% of normal for a GFR of 10 to 20 mL/min, and to 25% of normal for a GFR <10 mL/min
  • There is little, if any, true metabolism of carboplatin. Excretion is primarily by glomerular filtration in the urine, with most of the drug excreted in the first 6 hours. Approximately 32% of the dose is excreted unchanged.
  • Platinum from carboplatin slowly becomes protein bound, and is subsequently excreted with a terminal half-life of 5 days or more.