Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Sucrose
Succinic acid
Sodium hydroxide
Polysorbate 20

6.2   Incompatibilities
This medicinal product must not be mixed or diluted with other medicinal products except those mentioned in section 6.6.
Glucose (5%) solution should not be used for reconstitution or dilution since it causes aggregation of the protein.

Kadcyla PI Version 6
6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
Shelf-life of the Reconstituted solution

Chemical and physical in-use stability of the reconstituted solution has been demonstrated for up to 24 hours at 2°C to 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the reconstituted vials can be stored for up to 24 hours at 2°C to 8°C, provided it was reconstituted under controlled and validated aseptic conditions, and must be discarded thereafter.

Shelf-life of the Diluted solution

The reconstituted Kadcyla solution diluted in infusion bags containing sodium chloride 9 mg/mL (0.9%) solution for infusion, or sodium chloride 4.5 mg/mL (0.45%) solution for infusion, is stable for up to 24 hours at 2°C to 8°C, provided it was prepared under controlled and validated aseptic conditions. Particulates may be observed on storage if diluted in 0.9% sodium chloride (see section 6.6).

6.4   Special precautions for storage

Store in a refrigerator (2°C – 8°C).
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5   Nature and contents of container

Kadcyla 100 mg powder for concentrate for solution for infusion
Kadcyla is provided in 15 mL (100 mg) Type 1 glass vial closed with a grey-butyl rubber stopper coated with fluoro-resin laminate, and sealed with an aluminium seal with a white plastic flip-off cap.

Pack of 1 vial.

Kadcyla 160 mg powder for concentrate for solution for infusion
Kadcyla is provided in 20 mL (160 mg) Type 1 glass vial closed with a grey-butyl rubber stopper coated with fluoro resin laminate, and sealed with an aluminium seal with a purple plastic flip-off cap.

Pack of 1 vial.

6.6   Special precautions for disposal and other handling
Appropriate aseptic technique should be used. Appropriate procedures for the preparation of chemotherapeutic medicinal products should be used.

The reconstituted Kadcyla solution should be diluted in polyvinyl chloride (PVC) or latex-free PVC-free polyolefin infusion bags.

The use of 0.20 or 0.22 micron in-line polyethersulfone (PES) filter is required for the infusion when the concentrate for infusion is diluted with sodium chloride 9 mg/mL (0.9%) solution for infusion.
In order to prevent medicinal product errors it is important to check the vial labels to ensure that the medicinal product being prepared is Kadcyla (trastuzumab emtansine) and not another trastuzumab- containing product (e.g. trastuzumab or trastuzumab deruxtecan).
Kadcyla PI Version 6
Instructions for reconstitution

•    100 mg trastuzumab emtansine vial: Using a sterile syringe, slowly inject 5 mL of sterile water for injection into the vial.
•    160 mg trastuzumab emtansine vial: Using a sterile syringe, slowly inject 8 mL of sterile water for injection into the vial.
•    Swirl the vial gently until completely dissolved. Do not shake.

Reconstituted solution should be inspected visually for particulate matter and discolouration prior to administration. The reconstituted solution should be free of visible particulates, clear to slightly opalescent. The colour of the reconstituted solution should be colourless to pale brown. Do not use if the reconstituted solution contains visible particulates, or is cloudy or discoloured.

Instructions for dilution

Determine the volume of the reconstituted solution required based on a dose of 3.6 mg trastuzumab emtansine/kg body weight (see section 4.2):

Volume (mL) = Total dose to be administered (body weight (kg) x dose (mg/kg)) 20 (mg/mL, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial and added to an infusion bag containing 250 mL of sodium chloride 4.5 mg/mL (0.45%) solution for infusion or sodium chloride 9 mg/mL (0.9%) solution for infusion. Glucose (5%) solution should not be used (see section 6.2).
Sodium chloride 4.5 mg/mL (0.45%) solution for infusion may be used without a polyethersulfone (PES) 0.20 or 0.22-μm in-line filter. If sodium chloride 9 mg/mL (0.9%) solution for infusion is used for infusion, a 0.20 or 0.22 micron in-line polyethersulfone (PES) filter is required. Once the infusion is prepared it should be administered immediately. Do not freeze or shake the infusion during storage.

Disposal

The reconstituted product contains no preservative and is intended for single use only. Discard any unused portion.

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

7.     MARKETING AUTHORISATION HOLDER

Roche Pharmaceuticals (Israel) Ltd., P.O. Box 6391, Hod Hasharon, 4524079.
8.     MARKETING AUTHORISATION NUMBER(S)

151.63.33939.00