Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sucrose.
Potassium dihydrogen phosphate.
Phosphoric acid (for pH-adjustment).
Potassium hydroxide (for pH-adjustment).
Water for injection
6.2 Incompatibilities
Yondelis 1mg must not be mixed or diluted with other medicinal products except those mentioned in Section 6.6
.

6.3 Shelf life
The expiry date of the product is indicated on the packaging materials.

After reconstitution
Chemical and physical stability has been demonstrated for 30 hours up to 25ºC.
After dilution
Chemical and physical stability has been demonstrated for
30 hours up to 25ºC.
From a microbiological point of view, the reconstituted solution should be diluted and used immediately. If not diluted and used immediately, in-use storage times and conditions prior to use of the reconstituted product are the responsibility of the user and would normally not be longer than 24 hours at 2ºC to 8ºC, unless reconstitution has taken place in controlled and validated aseptic conditions.

6.4 Storage conditions
Store in a refrigerator (2ºC - 8ºC).
For storage conditions of the reconstituted and diluted medicinal product, see section 6.3.

6.5 Nature and contents of container
Yondelis 1mg is supplied in a Type I colourless glass vial with a butyl rubber stopper covered with an aluminium flip-off seal.
Each vial contains 1 mg of trabectedin.
Each outer carton contains one vial.
 6.6 Special precautions for disposal and other handling

Preparation for intravenous infusion
Yondelis 1mg must be reconstituted and further diluted prior to intravenous infusion .
Yondelis reconstitution and dilution of the reconstituted solution must beconducted under aseptic conditions in a manner consistent with recommended safe procedures for handling cytotoxic compounds.

Instructions for reconstitution
Each vial containing 1 mg of trabectedin is reconstituted with 20 ml of sterile water for injections. The solution obtained has a concentration of 0.05 mg/ml and is for single-use only.

A syringe is used to inject 20 ml of sterile water for injections into the vial. Shake the vial until complete dissolution. The reconstituted solution results in a clear, colorless or slightly yellowish solution, essentially free of visible particles.

This reconstituted solution contains 0.05 mg/ml of trabectedin. It requires further dilution and is for single-use only.

Instructions for dilution
The reconstituted solution should be diluted with sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) solution for infusion. The required volume should be calculated as follows:

Volume (ml) = BSA (m2) x individual dose (mg/m2)
0.05 mg/ml

BSA = Body Surface Area
The appropriate amount of solution should be withdrawn from the vial and added to an infusion bag containing 500 ml of normal saline 0.9% solution for infusion or dextrose 5% solution for infusion if administration is to be made through a central venous line. If central venous access is not feasible and a peripheral venous line has to be used, the reconstituted solution may be further diluted in an infusion bag containing 1,000 ml of normal saline 0.9% solution for infusion or dextrose 5% solution for infusion.

Parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration,whenever solution and container permit. After reconstitution and dilution, chemical and physical stability has been demonstrated for 30 hours up to 25ºC. The reconstituted solution should be diluted and used immediately. The total elapsed time between initial reconstitution and end of treatment should not be longer than 30 hours.

Instructions for handling and disposal
Yondelis 1mg is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, caution should be exercised during handling. Procedures for proper handling and disposal of cytotoxic medicinal products must be followed. Yondelis should be handled and disposed of in a manner consistent with other anticancer drugs. Personnel should be trained in the correct techniques to reconstitute and dilute the medicinal product and should wear protective clothing including mask, goggles and gloves during the reconstitution and dilution. Pregnant staff must be excluded from working with this medicinal product.

Accidental contact with the skin, eyes or mucous membranes must be treated immediately with copious amounts of water.
No incompatibilities have been observed between Yondelis 1mg and type I glass bottles, polyvinylchloride (PVC) and polyethylene (PE) bags and tubing, polypropylene reservoirs and titanium implantable implantable vascular access systems.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.