Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients
Powder
Mannitol
Sucrose
Sodium chloride
Calcium chloride dihydrate
Glycylglycine
Methionine
Polysorbate 80
Hydrochloric acid (for pH-adjustment)
Sodium hydroxide (for pH-adjustment)

Solvent
Histidine
Hydrochloric acid (for pH-adjustment)
Sodium hydroxide (for pH-adjustment)
Water for injections

6.2   Incompatibilities
NovoSeven RT must not be mixed with infusion solutions or be given in a drip.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials 

In vial
After reconstitution, chemical and physical stability has been demonstrated for 6 hours at 25°C and 24 hours at 2°C-8°C .
From a microbiological point of view, the product should be used immediately. If not used immediately, storage time and storage conditions prior to use are the responsibility of the user, and should not be longer than 24 hours at 2°C-8°C , unless reconstitution has taken place in controlled and validated aseptic conditions. The reconstituted solution should be stored in the vial.

In syringe (50 ml polypropylene) in hospital settings only
Reconstitution must take place in controlled and validated aseptic conditions by adequately trained staff. Under these conditions, chemical and physical stability has been demonstrated for 24 hours at 25°C when stored in a 50 ml syringe (polypropylene). If not used immediately, the conditions prior to use are the responsibility of the user and the in-use storage time must not be longer than as stated above.

6.4   Special precautions for storage

–     Store powder and solvent below 25°C.
–     Store powder and solvent protected from light.
–     Do not freeze.
–     For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5   Nature and contents of container

The solvent of NovoSeven RT is provided in a pre-filled syringe.
The NovoSeven RT 1 mg (50 KIU) / NovoSeven RT 2 mg (100 KIU) package contains –     1 vial (2 ml) with white powder for solution for injection
–     1 pre-filled syringe (3 ml) with solvent for reconstitution
–     1 plunger rod
–     1 vial adapter, with an integrated particle filter with a pore size of 25 micrometer.

The NovoSeven RT 5 mg (250 KIU) package contains
–    1 vial (12 ml) with white powder for solution for injection
–    1 pre-filled syringe (10 ml) with solvent for reconstitution
–    1 plunger rod
–    1 vial adapter, with an integrated particle filter with a pore size of 25 micrometer.

Vial: Type I glass vial closed with a chlorobutyl rubber stopper, covered with an aluminium cap. The closed vial is equipped with a polypropylene tamper-evident snap-off cap.

Pre-filled syringe: Type I glass barrel with a polypropylene backstop and bromobutyl rubber plunger.
The syringe cap consists of bromobutyl rubber and polypropylene tamper evident seal.

Plunger rod: made of polypropylene.
6.6   Special precautions for disposal and other handling

The solvent of NovoSeven RT is provided in a pre-filled syringe. Handling procedures are described below.

Powder in vial and solvent in pre-filled syringe:

Always use an aseptic technique.


Reconstitution

•     The NovoSeven RT powder vial and pre-filled syringe with solvent should be at room temperature at reconstitution. Remove the plastic cap from the vial. If the cap is loose or missing, do not use the vial. Wipe the rubber stopper on the vial with a sterile alcohol swab and allow it to dry for a few seconds before use. Do not touch the rubber stopper after wiping it.

•     Remove the protective paper from the vial adapter. Do not take the vial adapter out of the protective cap. If the protective paper is not fully sealed or it is broken do not use the vial adapter. Turn over the protective cap, and snap the vial adapter onto the vial. Lightly squeeze the protective cap with the thumb and index finger. Remove the protective cap from the vial adapter.

•     Screw the plunger rod clockwise into the plunger inside the pre-filled syringe until resistance is felt. Remove the syringe cap from the pre-filled syringe by bending it down until the perforation breaks. Do not touch the syringe tip under the syringe cap. If the syringe cap is loose or missing, do not use the pre-filled syringe.

•     Screw the pre-filled syringe securely onto the vial adapter until resistance is felt. Hold the pre- filled syringe slightly tilted with the vial pointing downwards. Push the plunger rod to inject all the solvent into the vial. Keep the plunger rod pressed down and swirl the vial gently until all the powder is dissolved. Do not shake the vial as this will cause foaming.

If a larger dose is needed, repeat the procedure with additional vials, pre-filled syringes and vial adapters.

The NovoSeven RT reconstituted solution is colourless and should be inspected visually for particulate matter and discolouration prior to administration.

It is recommended to use NovoSeven RT immediately after reconstitution. For storage conditions of the reconstituted medicinal product, see section 6.3.

Administration

•     Keep the plunger rod pushed completely in. Turn the syringe with the vial upside down. Stop pushing the plunger rod and let it move back on its own while the reconstituted solution fills the syringe. Pull the plunger rod slightly downwards to draw the mixed solution into the syringe.

•     While holding the vial upside down, tap the syringe gently to let any air bubbles rise to the top.
Push the plunger rod slowly until all air bubbles are gone.

If the entire dose is not required, use the scale on the syringe to see how much mixed solution is withdrawn.

•     Unscrew the vial adapter with the vial.

•     NovoSeven RT is now ready for injection. Locate a suitable site, and slowly inject NovoSeven RT into a vein over a period of 2 – 5 minutes without removing the needle from the injection site.

Safely dispose of the used materials. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Procedure for pooling of vials for hospital use only:

During in vitro studies, the chemical and physical in-use stability has been demonstrated for 24 hours at 25°C in a 50 ml syringe (polypropylene). Compatibility with the product was demonstrated for the system consisting of a 50 ml syringe (polypropylene), a 2 m infusion tube (polyethylene) and an in- line filter with a 5 micrometer pore size.

Pooling of vials (hospital use only):

•     All steps should be completed under controlled and validated aseptic conditions by adequately trained staff.
•     If not reconstituted, pooled or used as recommended the in-use times and conditions prior to use are the responsibility of the user.
•     Ensure that a vial adapter is used •    Reconstitute the product as described above under Reconstitution Unscrew the empty syringe from the vial adapter and ensure that a vial adapter is attached to the vial containing reconstituted product.
•     Repeat the procedure with the appropriate number of additional vials, pre-filled syringes and vial adapters.
•     Draw approximately 5 ml of sterile air into the 50 ml syringe (polypropylene). Screw the syringe securely onto the vial adapter until resistance is felt. Hold the syringe slightly tilted with the vial pointing downwards. Push the plunger rod gently to inject a little air into the vial. Turn the syringe with the vial upside down and withdraw the contents of the vial into the syringe.
•     Repeat the above procedure with the remaining vials with reconstituted product, to obtain the desired volume in the syringe.
•     An in-line filter with a 5 micrometer pore size must be ensured for administration. Ensure that the syringe, the infusion tube and the in-line filter are primed and free of air before administration.
•     The syringe with adequately reconstituted product is now ready for administration in a CE- marked infusion pump (accepting a 50 ml syringe).
•     The infusion pump must only be operated by trained hospital personnel.


7.    REGISTRATION HOLDER:
Novo Nordisk Ltd.,
1 Atir Yeda St., Kfar-Saba 4464301


8.    MANUFACTURER:
Novo Nordisk A/S, Novo Allé
DK-2880 Bagsværd
Denmark