No long-term animal studies have been performed to establish the carcinogenic potential of trastuzumab, or to determine its effects on fertility in males.

6. Pharmaceutical particulars

6.1 List of excipients

L-histidine hydrochloride monohydrate

L-histidine

α,α-trehalose dihydrate

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

Unopened vials: 4 years.

After reconstitution with sterile water for injection 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 Ontruzant for intravenous 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 Ontruzant 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).

For storage conditions of the opened medicinal product, see section 6.3 and 6.6.

6.5 Nature and contents of container

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 Ontruzant is reconstituted with 7.2 mL of sterile water for injection (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 A volume overage of 4% ensures that the labelled dose of 150 mg can be withdrawn from each vial.

Ontruzant should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted solution may result in problems with the amount of Ontruzant that can be withdrawn from the vial.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 sterile water for injection in the vial containing the lyophilised Ontruzant, directing the stream into the lyophilised cake.

2) Swirl the vial gently to aid reconstitution. DO NOT SHAKE!