Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients

α,α-Trehalose dihydrate
L-Histidine hydrochloride monohydrate
L-Histidine
Polysorbate 20
6.2   Incompatibilities

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

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

KANJINTI should not be diluted 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:
KANJINTI 150 mg powder for concentrate for solution for infusion for single use 
After aseptic reconstitution with sterile water for injections, chemical and physical stability of the reconstituted solution has been demonstrated for 48 hours at 2°C - 8°C.

KANJINTI 420 mg powder for concentrate for solution for infusion for multiple use 
One vial of KANJINTI reconstituted with bacteriostatic water for injections may be stored for 28 days when refrigerated at 2°C - 8°C. The reconstituted solution contains a preservative and is therefore suitable for multiple doses. Any residual quantity of reconstituted solution should be discarded after 28 days.

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

Do not freeze the reconstituted solution.

Shelf-life following reconstitution and dilution:
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 KANJINTI has been demonstrated for up to 30 days at 2°C - 8°C, and subsequently for 24 hours at temperatures not exceeding 30°C.

From a microbiological point of view, the reconstituted solution and KANJINTI 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 - 8°C, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.
6.4   Special precautions for storage

Store in a refrigerator (2°C - 8°C).
Do not freeze the reconstituted solution.
Store in the original package in order to protect from light.

For storage conditions of the reconstituted medicinal product, see sections 6.3 and 6.6.
6.5   Nature and contents of container

KANJINTI 150 mg powder for concentrate for solution for infusion

20 mL clear glass type I vial with butyl rubber stopper laminated with a fluoro-resin film and aluminium seal flip-off dust cover containing 150 mg of trastuzumab.
Each carton contains one vial.

KANJINTI 420 mg powder for concentrate for solution for infusion

50 mL clear glass type I vial with butyl rubber stopper laminated with a fluoro-resin film and aluminium seal flip-off dust cover containing 420 mg of trastuzumab.

Each carton contains one vial.

6.6   Special precautions for disposal and other handling
Appropriate aseptic technique should be used for reconstitution and dilution procedures. Care must be taken to ensure the sterility of prepared solutions. Since the medicinal product does not contain any anti-microbial preservative or bacteriostatic agents, aseptic technique must be observed.

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.

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

The reconstituted solution should not be frozen.

KANJINTI 150 mg powder for concentrate for solution for infusion for single use 
Each 150 mg vial of KANJINTI is reconstituted with 7.2 mL of sterile water for injections (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 6.1. A volume overage of 4% ensures that the labelled dose of 150 mg can be withdrawn from each vial.


KANJINTI 420 mg powder for concentrate for solution for infusion for multiple use 
Each 420 mg vial of KANJINTI is reconstituted with 20 mL of bacteriostatic water for injections containing 1.1% benzyl alcohol (not supplied). Use of other reconstitution solvents should be avoided.

This yields a 21 mL solution, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.1. A volume overage of 5% ensures that the labelled dose of 420 mg can be withdrawn from each vial.

In the event of hypersensitivity to benzyl alcohol, water for injections (not supplied) may also be used to prepare a single dose. Such preparations must be used immediately, and any remaining material discarded. Other solvents should not be used.

KANJINTI vial              Volume of sterile water for            Final concentration injections / bacteriostatic water for injections
150 mg vial          +     7.2 mL                          =      21 mg/mL 420 mg vial          +     20 mL                           =      21 mg/mL

Instructions for aseptic reconstitution

1) Using a sterile syringe, slowly inject the appropriate volume (as noted above) of sterile water for injections / bacteriostatic water for injections in the vial containing the lyophilized KANJINTI, directing the stream into the lyophilized 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 KANJINTI results in a colorless 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) × 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) × 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 sodium chloride 9 mg/mL (0.9%) solution for injection. 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 medicinal products should be inspected visually for particulate matter and discoloration prior to administration.

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

7.    MARKETING AUTHORIZATION HOLDER

Amgen Europe B.V.
Minervum 7061
NL-4817 ZK Breda
The Netherlands