Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients
Herceptin® vial:
,-trehalose dihydrate
L-histidine hydrochloride
L-histidine polysorbate 20
Solvent vial: Water for Injection containing 1.1% benzyl alcohol (Bacteriostatic Water for Injection) 
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

Store vials at a refrigerator 2°C–8°C.
A vial of Herceptin® reconstituted with Bacteriostatic Water for Injection, as supplied, is stable for 28 days when stored refrigerated at 2°C–8°C.
The reconstituted solution contains preservative and is therefore suitable for multiple uses.
Any remaining reconstituted solution should be discarded after 28 days.
If Water for Injection without preservative is used, the reconstituted Herceptin solution should be used immediately and any unused portion discarded.
Use of other solvents for the reconstitution of Herceptin® should be avoided.

Do not freeze the reconstituted solution.

Solutions of Herceptin for infusion are stable in polyvinylchloride, polyethylene or polypropylene bags containing 0.9% sodium chloride at 2°C–8°C for 24 hours. Diluted Herceptin® has been shown to be physically and chemically stable for up to 24 hours at temperatures up to 300C. However, since diluted Herceptin contains effectively no preservative, the reconstituted and diluted solution should be stored refrigerated at 2°C–8°C. From a microbiological point of view, the Herceptin® infusion solution should 
be used immediately. The product is not intended to be stored after dilution unless the dilution has taken place under controlled and validated aseptic conditions.

6.5. Nature and contents of container

Herceptin vial:
A 50 ml clear glass type I vial with siliconised butyl rubber stopper for use with lyophilised formulations. Herceptin® is supplied as a sterile, lyophilised, white to pale yellow powder containing 440 mg of trastuzumab per vial.

Solvent vial: A 20 ml clear glass type I vial with butyl rubber stopper 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.

6.6. Instructions for use and handling

Preparation for Administration
Appropriate aseptic technique should be used.
Each vial of Herceptin 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.

HERCEPTIN should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted solution may result in problems with the amount of HERCEPTIN 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 Herceptin, 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 Herceptin 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).

7. LICENSE HOLDER
Roche Pharmaceuticals (Israel) Ltd., P.O.B. 6391, Hod Hasharon 4524079.

8. LICENSE NUMBER

Herceptin® 440mg I.V.              113 91 29676