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

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.

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