Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
L-Arginine hydrochloride
Phosphoric acid (for pH-adjustment)
Potassium hydroxide (for pH-adjustment)

6.2 Incompatibilities

This medicinal product 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.
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.


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

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

6.5 Nature and contents of container
Trabectedin Teva 0.25 mg
Type I colourless glass vial with a bromobutyl rubber stopper sealed with an aluminium flip-off cap with a teal polypropylene disk containing 0.25 mg of trabectedin.

Trabectedin Teva 1 mg
Type I colourless glass vial with a bromobutyl rubber stopper sealed with an aluminium flip-off cap with a pink polypropylene disk containing 1 mg of trabectedin.

Vials are sheathed in a protective sleeve (a clear, colourless, protective film covering around the vial (sleeving) to provide additional safety measures).

Each carton contains one vial.

6.6   Special precautions for disposal and other handling
Preparation for intravenous infusion
Trabectedin 0.25 mg and 1mg must be reconstituted and further diluted prior to intravenous infusion.
The reconstitution and dilution of the reconstituted solution must be conducted under aseptic conditions in a manner consistent with recommended safe procedures for handling cytotoxic compounds.

Instructions for reconstitution

Trabectedin Teva 0.25mg
Each vial containing 0.25 mg of trabectedin is reconstituted with 5 ml of 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 5 ml of sterile water for injections into the vial. The vial must be shaken until complete dissolution. The reconstituted solution results in a clear, colorless solution, free of visible particles.

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


Trabectedin Teva 1 mg
Each vial containing 1 mg of trabectedin is reconstituted with 20 ml of 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. The vial must be shaken until complete dissolution. The reconstituted solution results in a clear, colorless solution, 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 sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (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 should be further diluted in an infusion bag containing ≥ 1,000 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) solution for infusion.

Parenteral solutions should be inspected visually for particulate matter prior to administration.
Once the infusion is prepared, it should be administered immediately.

Instructions for handling and disposal
Trabectedin 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. Trabectedin 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 Trabectedin Teva 0.25 mg and 1 mg and type I glass bottles, polyvinylchloride (PVC) and polyethylene (PE) bags and tubing, polyisoprenereservoirs and titanium implantable vascular access systems.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.


7.   MANUFACTURER AND LICENSE HOLDER
Teva Israel Ltd.,
124 Dvora HaNevi'a St., Tel Aviv 6944020