KEMOCARB Concentrate for solution for infusion Ref.[50351] Active ingredients: Carboplatin

Dosage & Dose Modifications

Carboplatin should be used by intravenous route only. The recommended dose of carboplatin in previously untreated adults with normal renal function is 400mg/m² given as a single short-term intravenous infusion over 15 to 60 minutes. Alternatively see Formula dosing below.

Therapy should not be repeated until 4 weeks after the previous carboplatin course and/or until the neutrophil count is at least 2,000 cells/mm³ and the platelet count is at least 100,000 cells/mm³. Initial dosage should be reduced by 20-25% in patients with risk factors such as previous myelosuppressive therapy and/or poor performance status.

Determination of haematologic nadir by weekly blood counts during initial courses is recommended for future dosage adjustment and scheduling of carboplatin.

Impaired Renal Function

Patients with creatine clearance values below 60ml/min are at increased risk of severe myelosuppression. The frequency of severe leucopenia, neutropenia, of thrombocytopenia has been maintained at about 25% with the following dosage recommendations:

Insufficient data exists on the usage of carboplatin in patients with creatinine clearance of 15ml/min or less to permit a recommendation for treatment.

All the above dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance and to the acceptable level of myelosuppression.

Combination Therapy

The optimal use of carboplatin in combination with other myelosuppressive agents require dosage adjustments according to the regimen and schedule to be adopted.

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. The use of dosing formulae, as compared to empiric dose calculation based on body surface area allows for adjustment for patient variations in pretreatment renal function that might otherwise result in 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), as proposed by Calvert is:

Dose (mg) = (target AUC) x (GFR + 25)

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

An approach in heavily pretreated patients* receiving single agent carboplatin, when there is the desire to target a particular platelet nadir, is the use of the Egorin formula.

Dose (mg/m²) = 0.091{Cr. Clearance (ml/min)/BSA (mg/m²) [ {(Pretreatment platelet count-desired platelet nadir) x100/ Pretreatment platelet count}-17) + 86

^* Patients are considered heavily pretreated if they have received any of the following: mitomycin-C, nitrosoureas, combination therapy with doxorubicin, cyclophosphamide and cisplatin; chemotherapy with 5 or more different agents; or radiotherapy ≥4,500 rads to a single port 20x20 cm or more than one field of therapy.

Preparation of intravenous solution

KEMOCARB (Carboplatin aqueous solution) Injection is a premixed aqueous solution of 10mg/ml Carboplatin. KEMOCARB aqueous solution 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 prepared as directed, KEMOCARB aqueous 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 aqueous solutions be discarded 8 hours after dilution.

There is no known antidote for carboplatin Injection overdosage. The anticipated complications of overdosage would be secondary to bone marrow suppression and/or hepatic toxicity.

Store below 30°C. Do not freeze. Protect from light.

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Use of 5% sodium hypochlorite solution is recommended as neutralizing agent in cases of Spills or leak of this solution.