Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients
Trazimera® 420 mg vial:
Sucrose
L-histidine hydrochloride monohydrate
L-histidine polysorbate 20
Solvent vial: Water for Injection containing 1.1% benzyl alcohol (Bacteriostatic Water for Injection) 
Trazimera® 150 mg vial
Sucrose
2022-0077320
 L-histidine hydrochloride monohydrate
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.

6.4. Special precautions for storage



Shelf life after opening
Stability of reconstituted solution and infusion solution
Any residual quantities of reconstituted solutions and infusion solutions that have not been produced under controlled and validated aseptic conditions must be discarded.

Trazimera® 150 mg for single dosing and Trazimera® 420 mg for single dosing when reconstituted with sterile water for injection
Trazimera® 150 mg is intended to be reconstituted with sterile water for injection for single dosing. Trazimera® 420 mg may be reconstituted with sterile water for injection, instead of the supplied bacteriostatic water for injection, in which case, it is only for single dosing.
Stability of the reconstituted concentrate of Trazimera® 150 mg and Trazimera® 420 mg when sterile water for injection is used
After reconstitution with sterile water for injection, the reconstituted concentrate is physically and chemically stable for up to 48 hours at 2 °C to 8 °C.
For microbiological reasons, the reconstituted concentrate should be immediately diluted further into the infusion solution. If it is not possible, in-use storage times and conditions of the ready solution before use are the responsibility of the user and should be no longer than 24 hours at 2 °C to 8 °C, unless the reconstitution has taken place in controlled and validated aseptic conditions.
Do not freeze the reconstituted concentrate.

Stability of the ready infusion solution of Trazimera® 150 mg and Trazimera® 420 mg when reconstituted with sterile water for injection
The ready Trazimera® infusion solution (diluted in 0.9% sodium chloride solution) is physically and chemically stable for up to 30 days at 2 °C to 8 °C and at temperatures up to 30 °C for 24 hours 
For microbiological reasons, the Trazimera® infusion solution should be used immediately. If it is not possible, in-use storage times and conditions of the infusion solution before use are the responsibility of the user and should be no longer than 24 hours at 2 °C to 8 °C, unless the reconstitution and dilution have taken place in controlled and validated aseptic conditions.

Trazimera® 420 mg for multiple dosing when reconstituted with the supplied bacteriostatic water for injection Stability of the reconstituted concentrate of Trazimera® 420 mg when bacteriostatic water for injection is used The Trazimera® concentrate, reconstituted with the bacteriostatic water for injection which is supplied with the Trazimera® 420 mg vial, is stable for 28 days when stored at 2 °C to 8 °C. It contains a preservative and is therefore suitable for multiple doses. Any residual quantity of the reconstituted concentrate should be discarded after 28 days.
For administration of Trazimera® to a patient with known hypersensitivity to benzyl alcohol (see section "Warnings and precautions section Trazimera® for multiple dosing (benzyl alcohol)"), Trazimera® should be reconstituted with sterile water for injection, withdrawing only one dose of Trazimera® from each vial. Residual quantities must be discarded. For the stability of the reconstituted concentrate and the infusion solution after reconstitution with sterile water for injection and dilution in 0.9% sodium chloride solution, see “Trazimera® 150 mg for single dosing and Trazimera® 420 mg for single dosing when reconstituted with sterile water for 2022-0077320
injection”.
Do not freeze the reconstituted concentrate. Protect from light.

Stability of the ready infusion solution of Trazimera® 420 mg when reconstituted with bacteriostatic water for injection
The ready Trazimera® infusion solution (diluted in 0.9% sodium chloride solution) is physically and chemically stable at temperatures up to 30 °C for 24 hours.
For microbiological reasons, the Trazimera® infusion solution should be used immediately. If it is not possible, in-use storage times and conditions of the infusion solution before use are the responsibility of the user. The in- use storage time should be no longer than 24 hours at 2 °C to 8 °C.

Disposal
After treatment or expiry, unused medicinal products must be returned in the original packaging to the place where dispensed (doctor or pharmacist) for proper disposal.

Special precautions for storage
Store in the refrigerator (2 8 °C).
Keep out of the reach of children.
Unopened vials of Trazimera® may be stored at room temperature (up to 30 °C) in the original packaging protected from light for a single period of up to 3 months. Once removed from refrigeration and stored under these conditions, discard after 3 months.

6.5. Nature and contents of container

Trazimera® 420mg vial:
A clear glass type I vial. Herceptin 420mg is supplied as a sterile, lyophilised, white powder containing 420 mg of trastuzumab per vial.

Solvent vial: A clear glass type I vial containing 20 ml sterile Bacteriostatic Water for Injection, containing 1.1% benzyl alcohol as an antimicrobial preservative.
Each carton contains one vial of Herceptin (trastuzumab) and one vial of solvent.

Trazimera® 150mg vial:
A clear glass type I vial. Herceptin 150mg is supplied as a sterile, lyophilised, white powder containing 150 mg of trastuzumab per vial.


6.6. Instructions for use and handling
Preparation for Administration
Appropriate aseptic technique should be used.
Each vial of Trazimera® 420 mg is reconstituted with 20 ml of Bacteriostatic Water for Injection, as supplied. This yields a solution for multiple use, containing 21 mg/ml trastuzumab, at a pH of approximately 6.0.
The reconstituted preparation results in a colourless to pale yellow transparent solution. Water for Injection (not supplied) may also be used for single-dose preparation. Use of other reconstitution solvents should be avoided.

Trazimera® 420 mg and Trazimera® 150 mg should be carefully handled during reconstitution.
Causing excessive foaming during reconstitution or shaking the reconstituted solution may result in problems with the amount of Trazimera® 420 mg and Trazimera® 150 mg that can be withdrawn from the vial.

Reconstitution:
1) Using a sterile syringe, slowly inject 20 mL of Bacteriostatic Water for Injection into the vial containing the lyophilised Trazimera® 420 mg , 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 2022-0077320
approximately 5 minutes. The reconstituted Trazimera® 420 mg          results in a colourless to pale yellow transparent solution and should be essentially free of visible particulates.

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. Once the infusion is prepared it should be administered immediately (see 6.3 Special precautions for storage).