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4.2. Posology and method of administration
The following paragraph has also been deleted from 4.2:
Specific dosage recommendations for use in children and infants cannot be made due to insufficent use in paediatrics at this time.
Highlighted paragraph added to section
Dosage and Administration
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, the Calvert formula shown below may be used to determine dosage:
Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25]
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Target AUC
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Planned Chemotherapy
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Patient Treatment status
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5-7 mg/ml.min
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single agent carboplatin
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previously untreated
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4-6 mg/ml.min
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single agent carboplatin
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previously treated
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4-6 mg/ml.min
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carboplatin plus cyclophosphamide
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previously untreated
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Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.
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: In patients with impaired renal function, dosage of carboplatin should be reduced (refer to Calvert formula) and haematological nadirs and renal function monitored.
Combination Therapy
The optimal use of carboplatin in combination with other myelosuppressive agents requires dosage adjustments according to the regimen and schedule to be adopted.
Elderly
Dosage adjustment may be necessary in elderly patients.
Paediatric patients:
There is insufficient information to support a dosage recommendation in the paediatric population.
5.1. Pharmacodynamic properties
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ATC Code: Antineoplastic agent LO1X A02
Carboplatin, like Cisplatin, interferes with DNA intrastrand and interstrand crosslinks in cells exposed to the drug. DNA reactivity has been correlated with cytotoxicity.
Paediatric patients:
Safety and efficacy in children have not been established.
5.2. Pharmacokinetic properties
HIghlighted paragraph added to section
After a 1-hour infusion (20-520mg/m2), plasma levels of total platinum and free (ultrafilterable) platinum decay biphasically following first order kinetics. For free platinum, the initial phase (t alpha) half life is approximately 90 minutes and the later phase (t beta) half life approximately 6 hours. All free platinum is in the form of carboplatin in the first 4 hours after administration.
Carboplatin is excreted primarily by glomerular filtration in urine, with recovery of 65% of a dose within 24 hours. Most of the drug is excreted within the first 6 hours. Approximately 32% of a given dose of carboplatin is excreted unchanged.
Protein binding of carboplatin reaches 85-89% within 24 hours of administration, although during the first 4 hours, only up to 29% of the dose is protein bound. Patients with poor renal function may require dosage adjustments due to altered pharmacokinetics of carboplatin.
Carboplatin clearance has been reported to vary by 3- to 4- fold in paediatric patients. As for adult patients, literature data suggest that renal function may contribute to the variation in carboplatin clearance.
10. DATE OF REVISION OF THE TEXT
date change
19 May 2009
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