Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1     List of excipients

Concentrate
Dehydrated alcohol (ethanol, anhydrous) dl-alpha tocopherol (Vitamin E)
Propylene glycol
Anhydrous citric acid

Polysorbate 80
Polyethylene glycol 400 (Macrogol 400)
Dehydrated alcohol (ethanol, anhydrous)

6.2     Incompatibilities

This medicinal product must not be mixed with other medicinal products, except those mentioned in section 6.6.

Torisel 30 mg concentrate must not be added directly to aqueous infusion solutions. Direct addition of Torisel 30 mg concentrate to aqueous solutions will result in precipitation of medicinal product.

Always dilute Torisel 30 mg concentrate with 1.8 ml of the supplied diluent before adding to the infusion solution. The concentrate-diluent mixture may only be administered in sodium chloride 9 mg/ml (0.9%) solution for injection.

Torisel, when diluted, contains polysorbate 80, which is known to increase the rate of di-(2-ethylhexyl) phthalate extraction (DEHP) from polyvinyl chloride (PVC). This incompatibility has to be considered during the preparation and administration of Torisel. It is important that the recommendations in sections 4.2 and 6.6 be followed closely.

PVC bags and medical devices must not be used for the administration of preparations containing polysorbate 80, because polysorbate 80 leaches DEHP from PVC.

6.3     Shelf life

Unopened vial
The expiry date of the product is indicated on the packaging materials.
After first dilution of Torisel 30 mg concentrate with 1.8 ml of the supplied diluent 24 hours when stored below 25°C and protected from light.

After further dilution of the concentrate-diluent mixture with sodium chloride 9 mg/ml (0.9%) solution for injection
6 hours when stored below 25°C and protected from light.

6.4     Special precautions for storage

Store in a refrigerator (2°C - 8°C)
Do not freeze.

Keep the vials in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.
6.5       Nature and contents of container

Concentrate
Clear glass vial (type 1) with butyl rubber stopper and a plastic flip-top closure sealed with aluminum containing 1.2 ml of concentrate

Diluent
Clear glass vial (type 1) with butyl rubber stopper and a plastic flip-top closure sealed with aluminum containing 2.2 ml of diluent

Pack size: 1 vial of concentrate and 1 vial of diluent

6.6       Special precautions for disposal and other handling
During handling and preparation of admixtures, Torisel should be protected from excessive room light and sunlight.

Torisel, when diluted, contains polysorbate 80 and therefore appropriate administration materials must be used,
Therefore, PVC bags and medical devices must not be used for the preparation, storage and administration of Torisel solutions for infusions.

Bags/containers that come in contact with Torisel must be made of glass, polyolefin, or polyethylene.

Torisel concentrate and diluent should be inspected visually for particulate matter and discolouration prior to administration.
Do not use if particulates are present, or if discoloured. Use a new vial.

Dilution

The concentrate for solution for infusion must be diluted with the supplied diluent before administration in sodium chloride 9 mg/ml (0.9%) solution for injection.

Note: For MCL , multiple vials will be required for each dose over 25 mg. Each vial of Torisel must be diluted according to the instructions below. The required amount of concentrate-diluent mixture from each vial must be combined in one syringe for rapid injection into 250 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (see section 4.2).

The concentrate-diluent mixture should be inspected visually for particulate matter and discolouration.

Do not use if particulates are present, or if discoloured.
In preparing the solution, the following two-step process must be carried out in an aseptic manner according to local standards for handling cytotoxic/cytostatic medicinal products: 
STEP 1: DILUTION OF THE CONCENTRATE FOR SOLUTION FOR INFUSION WITH THE SUPPLIED DILUENT

•   Withdraw 1.8 ml of the supplied diluent.
•   Inject the 1.8 ml of diluent into the vial of Torisel 30 mg concentrate.
•   Mix the diluent and the concentrate well by inversion of the vial. Sufficient time should be allowed for air bubbles to subside. The solution should be a clear to slightly turbid, colourless to light-yellow to yellow solution, essentially free from visual particulates.


One vial of Torisel concentrate contains 30 mg of temsirolimus: when the 1.2 ml concentrate is combined with 1.8 ml of the supplied diluent, a total volume of 3.0 ml is obtained, and the concentration of temsirolimus will be 10 mg/ml. The concentrate-diluent mixture is stable below 25°C for up to 24 hours.

STEP 2: ADMINISTRATION OF CONCENTRATE FOR SOLUTION FOR INFUSION--DILUENT MIXTURE IN SODIUM CHLORIDE 9MG/ML (0.9%) SOLUTION FOR INJECTION

•   Withdraw the required amount of concentrate-diluent mixture (containing temsirolimus 10 mg/ml) from the vial; i.e., 2.5 ml for a temsirolimus dose of 25 mg.
•   Inject the withdrawn volume rapidly into 250 ml of sodium chloride 9 mg/ml (0.9%) solution for injection to ensure adequate mixing.

The admixture should be mixed by inversion of the bag or bottle, avoiding excessive shaking, as this may cause foaming.

The final diluted solution in the bag or bottle should be inspected visually for particulate matter and discolouration prior to administration. The admixture of Torisel in sodium chloride 9 mg/ml (0.9%) solution for injection should be protected from excessive room light and sunlight.

For MCL, multiple vials will be required for each dose over 25 mg.

Administration

•     Administration of the final diluted solution should be completed within six hours from the time that Torisel is first added to sodium chloride 9 mg/ml (0.9%) solution for injection.

•     Torisel is infused over a 30- to 60-minute period once a week. The use of an infusion pump is the preferred method of administration to ensure accurate delivery of the medicinal product.

•      Appropriate administration materials must be used to avoid excessive loss of medicinal product and to decrease the rate of DEHP extraction. The administration materials must consist of non- DEHP, non-PVC tubing with appropriate filter. An in-line polyethersulfone filter with a pore size of not greater than 5 microns is recommended for administration to avoid the possibility of particles bigger than 5 microns being infused. If the administration set available does not have an in-line filter incorporated, a filter should be added at the end of the set (i.e., an end-filter) before the admixture reaches the vein of the patient. Different end-filters can be used ranging in filter pore size from 0.2 microns up to 5 microns. The use of both an in-line and end-filter is not recommended (see sections 6.1 and 6.2).

•     Torisel, when diluted, contains polysorbate 80 ,and therefore appropriate administration materials must be used (see sections 6.1 and 6.2),. It is important that the recommendations in section 4.2 be followed closely.

Disposal

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