sfer studies. Herceptin is not genotoxic. A study of trehalose, a major formulation excipient did not reveal any toxicities.
No long-term animal studies have been performed to establish the carcinogenic potential of Herceptin, or to determine its effects on fertility in males.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
L-histidine hydrochloride
L-histidine
α,α-trehalose dihydrate
polysorbate 20
6.2 Incompatibilities
Herceptin should not be mixed or diluted with other 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
4 years
After reconstitution with water for injections the reconstituted solution is physically and chemically stable for 48 hours at 2°C – 8°C. Any remaining reconstituted solution should be discarded.
Solutions of Herceptin for infusion are physically and chemically stable in polyvinylchloride, polyethylene or polypropylene bags containing sodium chloride 9 mg/ml (0.9%) solution for injection for 24 hours at temperatures not exceeding 30°C.
From a microbiological point of view, the reconstituted solution and Herceptin infusion solution should be used immediately. The product is not intended to be stored after reconstitution and dilution unless this has taken place under controlled and validated aseptic conditions. If not used immediately, in-use storage times and conditions are the responsibility of the user.
6.4 Special precautions for storage
Store in a refrigerator (2°C – 8°C).
6.5 Nature and contents of container
Herceptin vial:
One 15 ml clear glass type I vial with butyl rubber stopper laminated with a fluoro-resin film containing 150 mg of trastuzumab.
Each carton contains one vial.
6.6 Special precautions for disposal and other handling
Appropriate aseptic technique should be used. Each vial of Herceptin is reconstituted with 7.2 ml of 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 6.0. A volume overage of 4 % ensures that the labelled dose of 150 mg can be withdrawn from each vial.
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reconstitution or shaking the reconstituted solution may result in problems with the amount of Herceptin that can be withdrawn from the vial.
The reconstituted solution should not be frozen.
Instructions for reconstitution:
1) Using a sterile syringe, slowly inject 7.2 ml of water for injections in 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:
• based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly dose of
