Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients
Herity vial:
D-sorbitol
Macrogol 3350 (Polyethylene Glycol – 3350)
L-Histidine hydrochloride monohydrate
L-Histidine
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment)

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 in the refrigerator at 2°C–8°C. Do not freeze.
A vial of Herity 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 Herity solution should be used immediately, and any unused portion discarded.
Use of other solvents for the reconstitution of Herity should be avoided.

Do not freeze the reconstituted solution.

Infusion solutions of Herity for intravenous infusion are stable for 24 hours at temperatures of 2°C to 8 °C in polyvinylchloride, or polyethylene bags containing 0.9 % sodium chloride solution injection.

6.5. Nature and contents of container

Herity vial:
A clear, colorless, 50 ml type I glass vial closed with a chlorobutyl rubber stopper. The rubber stopper is sealed with a flip-off cap. Herity is supplied as a sterile, lyophilised, off-white to pale yellow powder containing 420 mg of trastuzumab per vial.

Solvent vial: A clear, colorless, 20 ml type I glass vial with chlorobutyl rubber stopper sealed with a flip- off cap, containing 20 ml sterile Bacteriostatic Water for Injection, containing 1.1% benzyl alcohol as an antimicrobial preservative.

Each carton contains one vial of Herity (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 Herity 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 colorless to pale yellow transparent solution free of visible particles. Water for Injection (not supplied) may also be used for single-dose preparation. Use of other reconstitution solvents should be avoided.

Herity should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted solution may result in problems with the amount of Herity 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 powder of Herity, 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 Herity results in a colorless 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.