Carboplatin (Page 5 of 6)

Dose Adjustment Recommendations

Pretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.

The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.

Platelets Neutrophils Adjusted Dose * (From Prior Course)
> 100,000 > 2000 125%
50 to 100,000 500 to 2000 No Adjustment
< 50,000 <500 75%

*Percentages apply to Carboplatin Injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50 to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.

Carboplatin Injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.

Patients with Impaired Kidney Function

Patients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.

Baseline Creatinine Clearance Recommended Dose on Day 1
41 to 59 mL/min 250 mg/m 2
16 to 40 mL/min 200 mg/m 2

The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.

These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance based on the degree of bone marrow suppression.

Formula Dosing

Another approach for determining the initial dose of Carboplatin Injection is the use of mathematical formulae, which are based on a patient’s pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin (see CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).

A simple formula for calculating dosage, based upon a patient’s glomerular filtration rate (GFR in mL/min) and Carboplatin Injection target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51 Cr-EDTA clearance.

CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m 2.

The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.

AUC (mg/mL • min) % Actual Toxicity in Previously Gr 3 or Gr 4 Thrombocytopenia Treated Patients Gr 3 or Gr 4 Leukopenia
4 to 5 16% 13%
6 to 7 33% 34%

Geriatric Dosing

Because renal function is often decreased in elderly patients, formula dosing of carboplatin based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin AUCs and thereby minimize the risk of toxicity.

PREPARATION OF INTRAVENOUS SOLUTIONS:

Carboplatin Injection is a premixed aqueous solution of 10 mg/mL carboplatin.

Carboplatin Injection can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D 5 W) or 0.9% Sodium Chloride Injection, USP.

When prepared as directed, Carboplatin Injection solutions are stable for 8 hours at room temperature (25°C). Since no antibacterial preservative is contained in the formulation, it is recommended that Carboplatin Injection solutions be discarded 8 hours after dilution.

HOW SUPPLIED:

Product No. NDC No.
107205 63323-172-05 CARBOplatin Injection, 50 mg per 5 mL (10 mg per mL), in a 10 mL multiple dose vial packaged individually.
107215 63323-172-15 CARBOplatin Injection, 150 mg per 15 mL (10 mg per mL), in a 20 mL multiple dose vial packaged individually.
107245 63323-172-45 CARBOplatin Injection, 450 mg per 45 mL (10 mg per mL), in a 50 mL multiple dose vial packaged individually.
107260 63323-172-60 CARBOplatin Injection, 600 mg per 60 mL (10 mg per mL), in a 60 mL multiple dose vial packaged individually.

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