CARBOPLATIN Solution for infusion Ref.[6526] Active ingredients: Carboplatin

Dosage and Administration

Carboplatin should be used by the intravenous route only. The recommended dosage of Carboplatin in previously untreated adult patients with normal kidney function, i.e. creatinine clearance >60 ml/min is 400 mg/m² as a single short term IV dose administered by a 15 to 60 minutes infusion. 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]

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

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.

Initial dosage should be reduced by 20-25% in patients with risk factors such as previous myelosuppressive therapy and or poor performance status (ECOG-Zubrod 2-4 or Karnofsky below 80).

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

Needles or intravenous sets containing aluminium parts that may come in contact with carboplatin injection should not be used for preparation or administration. Aluminium reacts with carboplatin injection causing precipitate formation and/or loss of potency.

The safety measures for dangerous substances are to be complied with preparation and administration. Preparation must be carried out by personnel who have been trained in the safe use while wearing protective gloves, face mask and protective clothes.

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.

Patients with creatinine clearance below 60 ml/min are at increase risk of severe myelosuppression. The frequency of severe leukopenia, neutropenia, or thrombocytopenia has been maintained at about 25% with the following dosage recommendations:

Insufficient data exist on the use of carboplatin injection in patients with creatinine of 15 ml/min or less to permit a recommendation for treatment.

All of 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 requires dosage adjustments according to the regimen and schedule to be adopted.

Elderly

In patients of more than 65 years of age, adjustment of the carboplatin dose to the general condition is necessary during the first and the subsequent therapeutic courses.

Paediatric population

There is insufficient information to support a dosage recommendation in the paediatric population.

Dilution and Reconstitution

The product must be diluted prior to infusion, see section 6.6.

No overdosage occurred during clinical trials.

Symptoms

Symptoms may include myelosuppression, renal, hepatic and auditory function impairment. Reports of doses up to 1600mg/m² indicate patients feeling extremely ill with diarrhoea and alopecia developing. Use of higher than recommended doses of carboplatin has been associated with loss of vision (see section 4.4).

Management

There is no known antidote for carboplatin overdosage. If necessary, however, the patient may need supportive treatment relating to myelosuppression, renal, hepatic and auditory function impairment.

Shelf life

Unopened: 2 years.

After dilution:

In use: Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature and 30 hours at 2-8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions

Store below 25°C. Do not refrigerate or freeze.

Keep vial in the outer carton in order to protect from light.

For storage conditions of the diluted medicinal product, see section 6.3.

Carboplatin infusion is supplied in 5 ml/15 ml/50 ml/100 ml type I amber glass vial containing 5 ml/15 ml/45 ml/60 ml concentrate for solution respectively. Vials are closed using grey chlorobutyl rubber stopper/Grey Westar prewashed rubber stopper with an aluminium flip off seal.

1 glass vial in one monocarton
5 ml vial, containing 50mg of carboplatin, 10mg/ml.
15 ml vial, containing 150 mg of carboplatin, 10mg/ml.
50 ml vial, containing 450 mg carboplatin, 10mg/ml.
100 ml vial, containing 600 mg carboplatin, 10mg/ml.

Not all pack sizes may be marketed.

This product is for single dose use only.

Contamination

In the event of contact of carboplatin with eyes or skin, wash affected area with copious amounts of water or normal saline. A bland cream may be used to treat transient stinging of skin. Medical advice should be sought if the eyes are affected.

Disposal

Any unused product or waste material should be disposed of in accordance with local requirement.

Dilution

The product must be diluted prior to infusion, with 5 % dextrose solution or 0.9 % sodium chloride solution, to concentrates as low as 0.5 mg/ml.

Guidelines for the safe handling of anti-neoplastic agents:

1. Carboplatin should be prepared for administration only by professionals who have been trained in the safe use of chemotherapeutic agents
2. This should be performed in a designated area.
3. Adequate protective gloves should be worn.
4. Precautions should be taken to avoid the drug accidentally coming into contact with the eyes. In the event of contact with the eyes, wash with water and/or saline.
5. The cytotoxic preparation should not be handled by pregnant staff.
6. Adequate care and precautions should be taken in the disposal of items (syringes, needles, etc.) used to reconstitute cytotoxic drugs. Excess material and body waste may be disposed of by placing in double sealed polythene bags and incinerating at a temperature of 1,000 °C. Liquid waste may be flushed with copious amounts of water.
7. The work surface should be covered with disposable plastic-backed absorbent paper.
8. Use Luer-Lock fittings on all syringes and sets. Large bore needles are recommended to Minimise pressure and the possible formation of aerosols. The latter may also be reduced by the use of a venting needle.