Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients
Powder
Mannitol
Trehalose

Sodium chloride
Histidine
Tris (hydroxymethyl) aminoethane
Calcium chloride

Polysorbate 80
Glutathione (reduced)
Solvent
Sterilised water for injections

6.2   Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or solvents.

6.3 Shelf life
The expiry date of the product is indicated on the packaging materials.
After reconstitution, from a microbiological point of view, the product should be used immediately.
However, chemical and physical in-use stability has been demonstrated for 3 hours at 25°C.

During the shelf life, the product may be kept at room temperature (up to 25°C) for a single period not exceeding 6 months. The end of the 6 months storage at room temperature should be recorded on the product carton. The product may not be returned to refrigerated storage again.

6.4   Special precautions for storage

Store in a refrigerator (2°C – 8°C).
Do not freeze.
ADVATE with BAXJECT II device: Keep the product vial in the outer carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container
Both the powder vial and the vial containing 5 ml solvent are of type I glass closed with chlorobutyl or bromobutyl rubber stoppers. The product is provided in the following configuration: 
-     ADVATE with BAXJECT II device: Each pack contains a powder vial, a vial containing 5 ml solvent and a device for reconstitution (BAXJECT II).

6.6 Special precautions for disposal and other handling
ADVATE is to be administered intravenously after reconstitution of the product. The reconstituted solution should be inspected visually for any foreign particulate matter and/or discoloration.
 After reconstitution the solution should be clear,     colourless and free from foreign particles.
Do not use solutions that are cloudy or have deposits.
-      For administration the use of a luer-lock syringe is required.
-      Use within three hours after reconstitution.
-      Do not refrigerate the preparation after reconstitution.
-       Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Reconstitution with the BAXJECT II device

-        For reconstitution use only the sterilised water for injections and the reconstitution device provided in the pack.
-        Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or shows any sign of deterioration.
-        Aseptic Technique should be used


1.       If the product is still stored in a refrigerator, take both the ADVATE powder and solvent vials from the refrigerator and let them reach room temperature (between 15°C and 25°C).
2.       Wash your hands thoroughly using soap and warm water.
3.       Remove caps from powder and solvent vials.
4.       Cleanse stoppers with alcohol swabs. Place the vials on a flat clean surface.
5.       Open the package of BAXJECT II device by peeling away the paper lid without touching the inside (Fig. a). Do not remove the device from the package. Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or shows any sign of deterioration.
6.       Turn the package over and insert the clear plastic spike through the solvent stopper. Grip the package at its edge and pull the package off BAXJECT II (Fig. b). Do not remove the blue cap from the BAXJECT II device.
7.       For reconstitution only the sterilised water for injections and the reconstitution device provided in the pack should be used. With BAXJECT II attached to the solvent vial, invert the system so that the solvent vial is on top of the device. Insert the white plastic spike through the ADVATE powder stopper. The vacuum will draw the solvent into the ADVATE powder vial (Fig. c).
8.       Swirl gently until all material is dissolved. Be sure that the ADVATE powder is completely dissolved, otherwise not all reconstituted solution will pass through the device filter. The product dissolves rapidly (usually in less than 1 minute). After reconstitution the solution should be clear, colourless and free from foreign particles.

Fig. a                                             Fig. b                               Fig. c 


Administration
Use Aseptic Technique

Parenteral medicinal products should be inspected for particulate matter prior to administration, whenever solution and container permit. Only a clear and colourless solution should be used.

1.       Remove the blue cap from BAXJECT II. Do not draw air into the syringe. Connect the syringe to BAXJECT II/ (Fig. d).
2.       Invert the system (the vial with the reconstituted solution has to be on top). Draw the reconstituted solution into the syringe by pulling the plunger back slowly (Fig. e).
3.       Disconnect the syringe.
4.       Attach a butterfly needle to the syringe. Inject intravenously. The solution should be administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml per minute. The pulse rate should be determined before and during administration of ADVATE.
Should a significant increase occur, reducing the rate of administration or temporarily interrupting the injection usually allows the symptoms to disappear promptly (see sections 4.4 and 4.8).

Fig. d                               Fig. e