Zucarb

Zucarb

Carboplatin

Strength: 150 mg / 450mg

Pack Size: 1 vial

Drug Class: Antineoplastic agents, Platinum compounds

Dosage and Administration:

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)/ in general, however, single intermittent courses of Carboplatin Injection 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 advance ovarian cancer, an effective combination for previously untreated patients consists of:

Carboplatin Injection – 300 mg/m2 IV on day 1 every four weeks for six cycles (alternatively see Formula Dosing). Cyclophosphamide – 600mg/m2 IV on day 1 every four weeks for six cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES). Intermittent courses of Carboplatin Injection in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 10,000.

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 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)
*Percentages apply to Carboplatin Injection as a single agent or to both Carboplatin Injection 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.
>100,000	>2000	125%
50-100,000	500-2000	No Adjustment
<50,000	<500	75%

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

Patients with Impaired Kidney Function:

Patients with creatinine clearance values below 60mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent Carboplatin Injection 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 – 59 mL/min	250 mg/m2
16 – 40 mL/min	200 mg/m2

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

These dosing recommendations apply to the initial course of treatment. Subsequent dosages shluld 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 preexisting renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMOCOLOGY). 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 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/mLmin), has been proposed by Calvert. In these studies, GFR was measured by 51 Cr-EDTA clearance.

GALVERT FORMULA FOR CARBOPLATIN DOSING

Total Dose (mg) = (target AUC) X (GFR +25)

Note: With the Calvert formula, the total dose of Carboplatin Injection is calculated in mg, not mg/m2.

The target AUC of 4-6 mg/mLmin using single agent Carboplatin Injection 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 Injection administered to previously treated patients and the likelihood of developing toxicity.

% Actual Toxicity in Previously Treated Patients
	Gr 3 or Gr 4	Gr 3 or Gr 4
AUC (mg/mLmin)	Thrombocytopenia	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 Injection based on estimates of GFR should be used in elderly patients to provide predictable plasma Carboplatin Injection AUCs and thereby minimize the risk of toxicity.

PREPARATION OF INTRAVENOUS SOLUTIONS

Carboplatin Injection 10mg/mL is supplied as a Ready To Use (RTU) sterile solution in 5ml, 15ml, 45ml or 60ml vials. Total content of carboplatin per vial is described in following tableL

Vial Strength	Diluent Volume
50 mg	5 ml
150 mg	15 ml
450 mg	45 ml
600 mg	60 ml

Carboplatin Injection can be further diluted to concentrations as low as 0.5 mg/ml with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.

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

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Cold Storage: no