Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients
α,α-trehalose dihydrate
L-histidine hydrochloride
L-histidine polysorbate 20
6.2. Incompatibilities

This medicinal product must not be mixed or diluted with other medicinal products except those mentioned under section 6.6.

Do not dilute with glucose solutions since these cause aggregation of the protein.

6.3. Shelf life

The expiry date of the product is indicated on the packaging materials.

Aseptic reconstitution and dilution:
Shelf-life following reconstitution:

Herzuma 150mg powder for concentrate for solution for infusion for single-use After aseptic reconstitution with sterile water for Injection, chemical and physical stability of the reconstituted solution has been demonstrated for 7 days at 2°C-8°C

Herzuma 420mg powder for concentrate for solution for infusion for single-use or for multiple- use:

For single-use:
After aseptic reconstitution with sterile water for Injection, chemical and physical stability of the reconstituted solution has been demonstrated for 7 days at 2°C-8°C.

Do not freeze the reconstituted solution.

Herzuma for single-use contains no preservatives.
Any unused medicinal product or waste material should be disposed in accordance with local requirements.

For multiple-use;
Use appropriate aseptic technique when performing reconstitution with Bacteriostatic Water for Injection, containing 1.1% benzyl alcohol as a preservative. As the reconstituted solution contains a preservative it is therefore suitable for multiple-use. Store reconstituted Herzuma solution in the refrigerator at 2°C-8°C, for 28 days. Discard any unused Herzuma reconstituted solution after 28 days.

Do not freeze the reconstituted solution.

When administrating Herzuma to a patient with a known hypersensitivity to benzyl alcohol, Herzuma should be reconstituted with water for injections, with only one dose of Herzuma taken from each vial.
The reconstituted solution should be used immediately. Any remaining solution should be discarded.

Shelf-life following reconstitution and dilution;

Stability of ready infusion solution of Herzuma 150 mg and Herzuma 420 mg when reconstituted with Sterile Water for Injection (SWI):
After aseptic dilution in polyvinylchloride, polyethylene or polypropylene bags containing sodium chloride 9 mg/mL (0.9%) solution for injection, chemical and physical stability of Herzuma has been demonstrated for up to 30 days at 2°C-8°C, and 24 hours at temperatures not exceeding 30ºC.
From a microbiological point of view, the reconstituted solution and Herzuma infusion solution 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 not normally be longer than 24 hours at 2°C to 8°C, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.

Stability of Herzuma 420mg when reconstituted with Bacteriostatic Water for Injection (BWI) The solution of Herzuma for infusion diluted in polyvinylchloride or polyethylene bags containing 0.9% Sodium Chloride Injection, should be stored at 2°C to 8°C for no more than 24 hours prior to use.

Do not freeze.

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

6.4. Special precautions for storage

Store in a refrigerator (2°C–8°C).
Do not freeze the reconstituted solution.

For storage conditions after reconstituted / reconstituted and diluted medical product, see sections 6.3 and 6.6.
Keep out of the sight and reach of children.

6.5. Nature and contents of container

Herzuma 150 mg powder for concentrate for solution for infusion:
A 20 ml clear glass type I vial with fluroTec-coated butyl rubber stopper containing 150 mg trastuzumab.
Each carton contains one vial.

Herzuma 420 mg powder for concentrate for solution for infusion:

A 50 mL clear glass type I vial with butyl rubber stopper containing 420 mg of trastuzumab.
Each carton contains one vial.
6.6. Instructions for use and handling

Appropriate aseptic technique should be used for reconstitution and dilution procedures. Care must be taken to ensure the sterility of prepared solutions.

Aseptic preparation, handling, and storage:

Aseptic handling must be ensured when preparing the infusion. Preparation should be:
• performed under aseptic conditions by trained personnel in accordance with good practice rules especially with respect to the aseptic preparation of parenteral products.
• prepared in a laminar flow hood or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared solution for intravenous infusion to ensure maintenance of the aseptic conditions
Herzuma 150 mg powder for concentrate for solution for infusion

Each vial of Herzuma is reconstituted with 7.2 mL of sterile water for injection (not supplied). Use of other reconstitution solvents should be avoided.
This yields a 7.4 mL solution for single-dose use containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 4% ensures that the labelled dose of 150 mg can be withdrawn from each vial.

Herzuma 420 mg powder for concentrate for solution for infusion

Each vial of Herzuma is reconstituted with 20 mL of sterile water for injection or bacteriostatic water for injection (not supplied).
Use of other reconstitution solvents should be avoided.
This yields a 21 mL solution for single-dose use OR multiple-dose use, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 4% ensures that the labelled dose of 420 mg can be withdrawn from each vial.

Herzuma should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted solution may result in problems with the amount of Herzuma that can be withdrawn from the vial.

The reconstituted solution should not be frozen.

Instructions for aseptic reconstitution
1) Using a sterile syringe, slowly inject the appropriate volume (as noted above) of sterile water for injection/ bacteriostatic water for injection in the vial containing the lyophilised Herzuma, directing the stream into the lyophilised cake.
2) Swirl the vial gently to aid reconstitution. DO NOT SHAKE!

Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed for approximately 5 minutes. The reconstituted Herzuma results in a colourless to pale yellow transparent solution and should be essentially free of visible particulates.

Instructions for aseptic dilution of the reconstituted solution

Determine the volume of the solution required:
• based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly dose of 2 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) x dose (4 mg/kg for loading or 2 mg/kg for maintenance) 21 (mg/ml, concentration of reconstituted solution)

•   based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly dose of 6 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) x dose (8 mg/kg for loading or 6 mg/kg for maintenance) 21 (mg/ml, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to an infusion bag containing 250 ml of 0.9 % sodium chloride solution. Do not use with glucose-containing solutions (see Section 6.2).
The bag should be gently inverted to mix the solution in order to avoid foaming.
Parenteral solutions should be inspected visually for particulates and discoloration prior to administration.

No incompatibilities between Herzuma and polyvinylchloride, polyethylene or polypropylene bags have been observed.


7. REGISTRAION HOLDER
Padagis Israel Agencies Ltd., 1 Rakefet St., Shoham, Israel.
8. REGISTRATION NUMBER
Herzuma 150 mg: 168-26-36465
Herzuma 420 mg: 168-27-36466