CISPLATIN Concentrate for solution for infusion Ref.[6714] Active ingredients: Cis-Diaminedichloroplatinum

Posology

Adults and children

The cisplatin dosage depends on the primary disease, the expected reaction, and on whether cisplatin is used for monotherapy or as a component of a combination chemotherapy. The dosage directions are applicable for both adults and children. For recommendations on the dosage applicable, based on the diagnosis and the clinical condition, the current medical literature should be consulted.

For monotherapy, the following two dosage regimens are recommended:

Single dose of 50 to 120 mg/m² body surface every 3 to 4 weeks; 15 to 20 mg/m²/day for five days, every 3 to 4 weeks.

If cisplatin is used in combination chemotherapy, the dose of cisplatin must be reduced. A typical dose is 20 mg/m² or more once every 3 to 4 weeks unless in the combination therapy of small-cell and non-small-cell lung carcinoma, in which a typical dose of 80 mg/m² is administered.

Further dosage recommendations are to be based upon current medical insights, to be obtained from the literature or/and the appropriate working parties.

For warnings and precautions to be considered prior to the start of the next treatment cycle, see section 4.4.

In patients with renal dysfunction or bone marrow depression, the dose should be reduced adequately.

Method of administration

Cisplatin “Ebewe” 1mg/ml concentrate for solution for infusion is to be diluted before use (see section 6.6.).

The diluted solution should be administered only intravenously by infusion (see below). For administration, any device containing aluminium that may come in contact with cisplatin (sets for intravenous infusion, needles, catheters, syringes) must be avoided (see section 6.2.).

The cisplatin solution for infusion prepared according to instructions (see section 6.6.) should be administered by intravenous infusion over a period of 6 to 8 hours.

Adequate hydration must be maintained from 2 to 12 hours prior to administration until minimum 6 hours after the administration of cisplatin. Hydration is necessary to cause sufficient diuresis during and after treatment with cisplatin. It is realised by intravenous infusion of one of the following solutions:

• sodium chloride solution 0.9%;
• mixture of sodium chloride solution 0.9% and glucose solution 5% (1:1).

Hydration prior to treatment with cisplatin: Intravenous infusion of 100 to 200ml/hour for a period of 6 to 12 hours.

Hydration after termination of the administration of cisplatin: Intravenous infusion of another 2 litres at a rate of 100 to 200 ml per hour for a period of 6 to 12 hours.

Forced diuresis may be required should the urine secretion be less than 100 to 200 ml/hour after hydration. Forced diuresis may be realised by intravenously administering 37.5g mannitol as a 10% solution (375 ml mannitol solution 10%), or by administration of a diuretic if the kidney functions are normal. The administration of mannitol or a diuretic is also required when the administrated cisplatin dose is higher than 60 mg/m² of body surface.

It is necessary that the patient drinks large quantities of liquids for 24 hours after the cisplatin infusion to ensure adequate urine secretion.

CAUTION IS ESSENTIAL IN ORDER TO PREVENT AN INADVERTENT OVERDOSE.

An acute overdose of cisplatin may result in renal failure, liver failure, deafness, ocular toxicity (including detachment of the retina), significant myelosuppression, untreatable nausea and vomiting and/or neuritis. An overdose may be fatal.

There is no specific antidote in the event of a cisplatin overdose. Even if hemodialysis is initiated 4 hours after the overdose it has little effect on the elimination of cisplatin from the body due to a strong and rapid fixation of cisplatin to proteins.

Shelf life

Medicinal product as packaged for sale: 2 years.

Solution for infusion after dilution (see section 6.6):

Chemical and physical in-use stability has been demonstrated for 48 hours at 2 to 8°C when protected from light for solutions with a final cisplatin concentration of 0.1 mg/ml after dilution of the cisplatin 1mg/ml concentrate with one of the following solutions:

• sodium chloride solution 0.9%;
• mixture of sodium chloride solution 0.9% and glucose solution 5% (1:1);
• mixture of sodium chloride solution 0.9% and mannitol solution 5% (1:1).

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 to 8°C, unless reconstitution/dilution (etc) has taken place in controlled and validated aseptic conditions.

Medicinal product as packaged for sale:

Do not store above 25°C. Do not refrigerate or freeze. Keep the vial in the outer carton.

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

Amber type I glass vial with chlorobutyl rubber stopper with aluminium overseal.

Packs of 1, 5 or 10 vial(s) containing 10ml, 20 ml, 50 ml or 100 ml concentrate for solution for infusion each.

Not all pack sizes may be marketed.

The vials are packed with or without a protective plastic overwrap (OncoSafe).

Cisplatin 1 mg/ml concentrate for solution for infusion is to be diluted before use. For preparation of solution for infusion, any device containing aluminium that may come in contact with cisplatin (sets for intravenous infusion, needles, catheters, syringes) must be avoided (see section 6.2.).

Preparation of solution for infusion must take place in aseptic conditions.

For dilution of the concentrate, one of the following solutions should be used:

- sodium chloride solution 0.9%;

- mixture of sodium chloride solution 0.9% and glucose solution 5% (1:1) (resulting final concentrations: sodium chloride 0.45%, glucose 2.5%).

- Should hydration prior to the treatment with cisplatin be impossible, the concentrate may be diluted with:

- mixture of sodium chloride solution 0.9% and mannitol solution 5% (1:1) (resulting final concentrations: sodium chloride 0.45%, mannitol 2.5%).

Preparation of cisplatin solution for infusion:

The required amount (dose) of the cisplatin concentrate 1 mg/ml calculated according to the instructions in section 4.2. should be diluted in 1-2 litres of one of the above mentioned solutions.

The diluted solution should be administered only by intravenous infusion (see section 4.2.).

Only clear and colourless to yellowish solutions without visible particles should be used.

For single use only.

Cytotoxic agents should be prepared for administration only by personnel who have been trained in the safe handling of the preparation.

Refer to local cytotoxic handling guidelines.

As any other cytotoxic agent, cisplatin should be used with extreme caution: gloves, face masks and protective clothing are required and vital. Cisplatin should be processed under a protective hood, if possible. Contact with skin and/or mucous membranes must be avoided. Pregnant hospital employees should not work with cisplatin.

Skin contact: Rinse with large quantities of water. Apply an ointment if you have a temporary burning feeling. (Note: Some persons are sensitive to platinum and may experience a skin reaction).

In the event of spillage, operators should put on gloves and mop up the spilled material with a sponge kept in the area for that purpose. Rinse the area twice with water. Put all solutions and sponges into a plastic bag and seal it. In the case of spillage all items coming into contact with Cisplatin should be handled and disposed in accordance to local cytotoxic guidelines.

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