Pharmaceutical particulars : מידע רוקחי

6.      PHARMACEUTICAL PARTICULARS

6.1   List of excipients
Solvent (syringe A):       75:25 Poly (DL-lactide-co-glycolide)
N-methyl-2-pyrrolidone

Powder (syringe B):        None

6.2   Incompatibilities
The leuprorelin present in syringe B must only be mixed with the solvent in syringe A and must not be mixed with other medicinal products.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
Once outside the refrigerator this product may be stored in its original packaging below 25°C for up to four weeks. Afterward dispose of the product. Do not return to refrigerator.

After first opening of the tray, the powder and solvent for solution for injection are to be immediately reconstituted and administered to the patient.

Once reconstituted: use immediately, as the viscosity of the solution increases with time.

6.4   Special precautions for storage
Store in a refrigerator (2°C – 8°C); in the original package in order to protect from moisture.
This product must be at room temperature prior to injection. Remove from the refrigerator approximately 30 minutes before use.
Once outside the refrigerator this product may be stored in its original packaging below 25°C for up to four weeks. Afterward dispose the product. Do not return to refrigerator.

6.5        Nature and contents of container

Two pre-filled syringes, one cyclic olefin copolymer syringe containing powder (Syringe B), and one polypropylene syringe containing solvent (Syringe A). Together the two syringes comprise a mixing system.

Syringe A has a plunger tip of thermoplastic rubber and is capped with a polyethylene or polypropylene Luer-Lock cover. The syringe tip cap and the two plunger tips of Syringe B are composed of chlorobutyl rubber.

The following pack sizes are available:

•   A kit consisting of two thermoformed trays in a cardboard carton. One tray contains one pre- filled polypropylene syringe A, a large plunger rod and a desiccant pouch. The other tray contains pre-filled cyclic olefin copolymer syringe B, a 20-gauge sterile needle and a silicone desiccant pouch.

6.6       Special precautions for disposal and other handling

Allow the product to come to room temperature by removing from the refrigerator approximately 30 minutes prior to use.
Please prepare the patient for injection first, followed by the preparation of the product, using the instructions below. If the product is not prepared using the proper technique, it should not be administered, as lack of clinical efficacy may occur due to incorrect reconstitution of the product.

Step 1: Open both trays (tear off the foil from the corner which can be recognized by a small bubble) and empty the contents onto a clean field (two trays containing Syringe A (Figure 1.1) and Syringe B (Figure 1.2)). Discard the desiccant pouches.



Step 2: Pull out and do not unscrew the blue coloured short plunger rod together with the attached grey stopper from Syringe B and discard (Figure 2). Do not attempt to mix the product with two stoppers in place.
Step 3: Gently screw the Syringe B white plunger rod to the remaining grey stopper in Syringe B (Figure 3).



Step 4: Remove the grey rubber cap from Syringe B and put down the Syringe (Figure 4).



Step 5: Hold Syringe A in a vertical position to ensure no liquid leaks out and unscrew the clear cap from Syringe A (Figure 5).



Step 6: Join the two syringes together by pushing in and twisting Syringe B onto Syringe A until secure (Figure 6a and 6b). Do not over tighten.
Step 7: Flip the connected unit over and continue to hold the syringes vertically with Syringe B on the bottom while injecting the liquid contents of Syringe A into Syringe B containing the powder (leuproreline acetate) (Figure 7).



Step 8: Thoroughly mix the product by gently pushing the contents of both syringes back and forth between syringes (60 times in total, which takes approximately 60 seconds) in a horizontal position to obtain a homogenous, viscous solution (Figure 8). Do not bend the syringe system (please note that this may cause leakage as you may partially unscrew the syringes).



When thoroughly mixed, the viscous solution will appear with a colour in the range of colourless to white to pale yellow (which could include shades of white to pale yellow).
Important: After mixing proceed with the next step immediately as the product gets more viscous over time. Do not refrigerate the mixed product.

Please note: Product must be mixed as described; shaking WILL NOT provide adequate mixing of the product.


Step 9: Hold the syringes vertically with Syringe B on the bottom. The syringes should remain securely coupled. Draw the entire mixed product into Syringe B (short, wide syringe) by pushing down the Syringe A plunger and slightly withdrawing the Syringe B plunger (Figure 9).



Step 10: Twist off Syringe A while continuing to push down on the Syringe A plunger (Figure 10).
Ensure that no product leaks out as the needle will then not secure properly when attached.

Please note: one large or a few small air bubbles may remain in the formulation - this is acceptable.
Please do not purge the air bubbles from Syringe B at this stage as product may be lost! Step 11:
• Hold Syringe B upright and hold back the white plunger to prevent loss of the product.
• Open pack of the safety needle by peeling back paper tab and take out safety needle.
• Secure the safety needle to Syringe B by holding the syringe and gently turning the needle clockwise with approximately a three-quarter turn until the needle is secure (Figure 11).
Do not over tighten as this may cause cracking of the needle hub resulting in leakage of the product during injection.
Should the needle hub crack, appear to be damaged, or have any leakage, the product should not be used. The damaged needle should not be substituted/replaced and the product should not be injected.
The entire product should be disposed of securely

In the event of damage to the needle hub, a new replacement product should be used.



Step 12: Pull off the protective needle cover prior to administration (Figure 12).
Important: Do not operate the safety needle mechanism before administration.


Step 13: Prior to administration, purge any large air bubbles from Syringe B. Administer the product subcutaneously. Please ensure that the full amount of the product in Syringe B is injected.
Step 14: After injection, lock the safety shield using any of the activation methods listed below.

1. Closure on a flat surface

Press the safety shield, lever side down, onto a flat surface (Figure 14.1a and b) to cover the needle and lock the shield.
Verify locked position through audible and tactile “click”. Locked position will completely cover needle tip (figure 14.1b).



2. Closure with your thumb

Placing your thumb on the safety shield (Figure 14.2a), cover the needle tip and lock the shield.
Verify locked position through audible and tactile “click”. Locked position will completely cover needle tip (figure 14.2b).



Step 15: Once safety shield is locked, immediately dispose of the needle and syringe in an approved sharps container.