Posology : מינונים

4.2   Posology and method of administration
Carboplatin Teva Injection does not contain any antimicrobial preservative; it is intended for single- dose administration only.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Administration
This preparation is intended for intravenous use only, usually by an infusion lasting 15 minutes or longer. It may be given to outpatients since hydration is not required.
Aluminium reacts with carboplatin causing precipitate formation and loss of potency; therefore, needles or intravenous sets containing aluminium parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin.
Therapy should not be repeated until four 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.
Therapy with carboplatin should be discontinued in the case of an unresponsive tumour, progressive disease and/or occurrence of not tolerable side effects.


Carboplatin Teva MF 05/2020 Notification CLEAN
Reduction of the initial dosage by 20-25% is recommended for those patients who present with risk factors such as prior myelosuppressive treatment and low performance status (ECOG-Zubrod 2 - 4 or Karnofsky below 80).

Determination of the haematological nadir by weekly blood counts during the initial courses of treatment with carboplatin is recommended for future dosage adjustment.

Dosage
Advanced ovarian carcinoma:
Initial Treatment
In patients with advanced ovarian carcinoma, carboplatin administered in combination therapy as established by specialists, is recommended at a dosage of 300 mg/m2 I.V. on day 1 every 4 weeks for six cycles.

Secondary treatment
Carboplatin, as monotherapy, has been shown to be effective in patients with recurrent ovarian carcinoma. The recommended dosage is 360 mg/m2 I.V. on day 1 every 4 weeks.

Metastatic small cell carcinoma of the lung:
The recommended dosage is 400 mg/m2 as a single I.V. dose administered by a short-term (15 - 60 minutes) infusion. Therapy should not be repeated until 4 weeks after the previous carboplatin course.
The optimal use in combination with other myelosuppressive agents requires dosage adjustments according to the regimen and schedule to be adopted.

Impaired renal function
Patients with creatinine clearance values of less than 60 ml/min are at greater risk of severe myelosuppression.

The optimal use of carboplatin in patients presenting with renal impairment requires adequate dosage adjustment and frequent monitoring of haematological nadirs, electrolytes and renal function.

The onset of severe leucopenia, neutropenia or thrombocytopenia may be controlled using the following posology:
- 250 mg/m² I.V. on day 1, in patients with creatinine clearance base values from 41 - 59 ml/min.
- 200 mg/m² I.V. on day 1, in patients with creatinine clearance base values from 21 - 40 ml/min.

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.

In general, intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 cells/mm3 and platelet count is at least 100,000 cells/mm3 (see under decreased platelet and neutrophil counts).
Carboplatin should not be administered to patients with a creatinine clearance  20 ml/min.

Dose recommendations according to AUC
Alternatively, the initial dose can be calculated using the Calvert formula. This is based on renal function (glomerular filtration rate [GFR]). Thereby, the risk of underdosing or overdosing due to individual differences in renal function is reduced.
Calvert formula: total dose (mg) = (target AUC*)  (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.


Carboplatin Teva EM 12/2023 Notification
*Target AUC                     Planned chemotherapy                 Pre-treatment status 5-7 mg/ml min                  Single agent carboplatin                 No prior therapy                4-6 mg/ml min                  Single agent carboplatin                 Prior therapy
4-6 mg/ml min               Carboplatin plus cyclophosphamide           No prior therapy


The Calvert formula should not be used in heavily pre-treated patients who have already received one of the following regimens:
- Mitomycin C
- Nitrosourea
- Doxorubicin/cyclophosphamide/cisplatin combination chemotherapy
- Combination therapy including 5 or more cytostatic agents
- Radiation therapy  5,000 rad focused on a field of 20  20 cm or more than one field.

Decreased platelet and neutrophil counts
For patients who experience no hematologic toxicity (i.e., platelet and neutrophil counts remain above 100,000 and 2,000/mm3, respectively) with the previous dose, dosage of carboplatin in single or combination (e.g., cyclophosphamide) therapy may be increased by 25%. For patients who experience only mild to moderate hematologic toxicity (i.e., platelet or neutrophil counts of 50,000-100,000 or 500-2,000/mm3, respectively) with the previous dose, dosage adjustment is not necessary in single agent or combination regimens. For patients who experience moderate to severe hematologic toxicity (e.g., platelet or neutrophil counts lower than 50,000 or 500/mm3, respectively) with the previous dose, consideration should be given to reducing the dosage of carboplatin in single agent or combination regimens by 25%. A summary of these dose adjustments is given in the table below: 
Platelets                       Neutrophils               Adjusted dose (from prior course) Greater than 100,000            Greater than 2,000        125%
50,000 – 100,000                500 – 2,000               No change Less than 50,000                Less than 500             75%

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.

Paediatric population
As no sufficient experience of carboplatin use in children is available, no specific dosage recommendations can be given.

Elderly (over 65 years old)
Dosage adjustment, initially or subsequently, may be necessary dependent on the physical condition of the patient.

Dilution
The product may be diluted with 5% Glucose for Injection or 0.9% Sodium Chloride for Injection to concentrations as low as 0.5 mg/ml (500 micrograms/ml).