Kemocarb Dosage/Direction for Use

Note: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of Carboplatin Injection.
Single-Agent Therapy: Carboplatin Injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m² IV on day 1 every 4 weeks (alternatively see Formula Dosing as follows). In general, however, single intermittent courses of Carboplatin should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 100,000.
Combination Therapy with Cyclophosphamide: In the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of: Carboplatin - 300 mg/m² IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing as follows); Cyclophosphamide - 600 mg/m² IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide, refer to its package insert.
Intermittent courses of Carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
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 as follows 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. (See Table 6.)

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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 as follows have been used. (See Table 7.)

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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 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. 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 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 ⁵¹Cr-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/m².
The target AUC of 4 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. (See Table 8.)

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Geriatric Dosing: Because renal function is often decreased in elderly patients, formula dosing of Carboplatin injection 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 Solution: KEMOCARB is a premixed aqueous solution of 10 mg/ml Carboplatin. KEMOCARB can be further diluted to concentrations between 0.5 mg/ml and 2.0 mg/ml with water for injection, or between 0.5 mg/ml and 7 mg/ml with 5% Dextrose or 0.9% Sodium Chloride. Chemical and physical in-use stability has been demonstrated below 25°C for 24 hours and at 2-8°C for 48 hours. However, from a microbiological point of view, the product should be used immediately.