Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1       List of excipients

Powder

Mannitol (E421)
Sucrose
Trometamol
Solvent

Water for injections

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

6.3       Shelf life

The expiry date of the product is indicated on the packaging materials.
Chemical and physical in-use stability has been demonstrated for 6 hours at temperatures of up to 25°C after reconstitution. From a microbiological point of view, the reconstituted medicinal product should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 6 hours at temperatures of up to 25°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

6.4       Special precautions for storage

Store in a refrigerator (2°C - 8°C). Do not freeze. Protect from light.
Before preparing the Enbrel solution, Enbrel may be stored outside of the refrigerator at temperatures up to a maximum of 25ºC for a single period of up to four weeks, after which it should not be refrigerated again. Enbrel should be discarded if not used within four weeks after removal from the refrigerator.

For storage conditions of the reconstituted medicinal product, see section 6.3.

6.5       Nature and contents of container
Clear glass vial (2 ml, type I glass) with rubber stoppers, aluminium seals, and flip-off plastic caps. Enbrel is supplied with pre-filled syringes containing water for injection. The syringes are type I glass. The syringe cover contains dry natural rubber (latex) (see section 4.4). Carton 
contains 4 vials of Enbrel with 4 pre-filled solvent syringes, 4 needles, 4 vial adaptors and 8 alcohol swabs.

6.6     Special precautions for disposal and other handling

Instructions for use and handling
Enbrel is reconstituted with 1 ml water for injections before use, and administered by subcutaneous injection. Enbrel contains no antibacterial preservative, and therefore, solutions prepared with water for injections should be administered as soon as possible and within 6 hours following reconstitution. The solution should be clear and colourless to pale yellow or pale brown, with no lumps, flakes or particles. Some white foam may remain in the vial – this is normal. Enbrel should not be used if all the powder in the vial is not dissolved within 10 minutes. If this is the case, start again with another vial.

Comprehensive instructions for the preparation and administration of the reconstituted Enbrel vial are given in the this leaflet, section 7, “INSTRUCTIONS FOR USE.” 
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7.    Instructions for use

This section is divided into the following sub-sections: a.    Introduction b.    Setting up for an injection c.    Preparing the Enbrel dose for injection d.    Adding solvent e.    Withdrawing the Enbrel solution from the vial f.    Placing the needle on the syringe g.    Choosing an injection site h.    Preparing the injection site and injecting the Enbrel solution i.    Disposing of supplies
 a.    Introduction

The following instructions explain how to prepare and inject Enbrel. Please read the instructions carefully and follow them step by step. You will be instructed by your doctor or his/her assistant on the techniques of self-injection or on giving an injection to a child. Do not attempt to administer an injection until you are sure that you understand how to prepare and give the injection.

This injection should not be mixed with any other medicine.
 b.    Setting up for an injection

•     Wash your hands thoroughly.
•     Select a clean well-lit, flat working surface.
•     The dose tray should contain the items listed below. (If not, don’t use the dose tray and consult your pharmacist). Use only the items listed. Do NOT use any other syringe.
1 Enbrel vial
1 Pre-filled syringe containing clear, colourless solvent (water for injections) 1 Needle

         1 Vial adaptor
2 Alcohol swabs
•     Inspect the expiry dates on both the vial label and the syringe label. They should not be used after the month and year shown.
 c.    Preparing the Enbrel dose for injection

•     Remove the contents of the tray
•     Remove the plastic cap from the Enbrel vial (see Diagram 1). Do NOT remove the grey stopper or aluminium ring around the top of the vial.

Diagram 1



•     Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the stopper with your hands or allow it to touch any surface.
•     Place the vial upright on a clean, flat surface.
•     Remove the paper backing from the vial adaptor package.
•     While still in the plastic package, place the vial adaptor on top of the Enbrel vial so that the vial adaptor spike is centered within the raised circle on top of the vial stopper (see Diagram 2).
•     Hold the vial firmly on the flat surface with one hand. With the other hand, push STRAIGHT DOWN FIRMLY on the adaptor package until you feel the adaptor spike penetrate the vial stopper and FEEL AND HEAR THE ADAPTOR RIM
LOCK INTO PLACE (see Diagram 3). Do NOT push down the adaptor at an angle (see Diagram 4). It is important that the vial adaptor spike completely penetrates the vial stopper.

Diagram 2.               Diagram 3.            Diagram 4.



CORRECT               INCORRECT

•     While holding the vial in one hand, remove the plastic packaging from the vial adaptor (see Diagram 5).


                                            Diagram 5.



•     Remove the protective cover from the syringe tip by breaking the white cap along the perforation. This is done by holding the collar of the white cap while grasping the end of the white cap with the other hand and bending it down and then up until it is broken (see Diagram 6). Do NOT remove the white collar that remains on the syringe.

Diagram 6



•     Do not use the syringe if this perforation is already broken. Start again with another dose tray.
•     Holding the glass barrel of the syringe (not the white collar) in one hand, and the vial adaptor (not the vial) in the other, connect the syringe to the vial adaptor by inserting the tip into the opening and turn clockwise until completely secured (see Diagram 7).

Diagram 7


 d.    Adding solvent

•     While holding the vial upright on the flat surface, push the plunger VERY SLOWLY until all the solvent is in the vial. This will help to reduce foaming (lots of bubbles) (see Diagram 8).
•     Once the solvent is added to the Enbrel, the plunger may move up by itself. This is due to air pressure and should not be of concern.


                                            Diagram 8



•     With the syringe still attached, gently move the vial in circles a few times, to dissolve the powder (see Diagram 9). Do NOT shake the vial. Wait until all the powder dissolves (usually less than 10 minutes). The solution should be clear and colourless to pale yellow or pale brown, with no lumps, flakes, or particles. Some white foam may remain in the vial this is normal. Do NOT use Enbrel if all the powder in the vial is not dissolved within 10 minutes. Start again with another dose tray.

Diagram 9


 e.    Withdrawing the Enbrel solution from the vial

•     With the syringe still attached to the vial and vial adaptor, hold the vial upside down at eye level. Push the plunger all the way into the syringe (see Diagram 10).

Diagram 10



•     Then, slowly pull the plunger back to draw the liquid into the syringe (see Diagram 11). For adult patients, withdraw the entire volume. For children, remove only the portion of liquid as directed by your child’s doctor. After you have withdrawn the Enbrel from the vial, you may have some air in the syringe. Do not be concerned, as you will remove the air in a later step.

Diagram 11




•     With the vial held upside down, unscrew the syringe from the vial adaptor by turning it anti-clockwise (see Diagram 12).

Diagram 12



•     Place the filled syringe on the clean, flat surface. Make sure that the tip does not touch anything. Be careful not to push down on the plunger.

(Note: After you have completed these steps, a small amount of liquid may remain in the vial.
This is normal.)
 f.    Placing the needle on the syringe

•     The needle has been placed in a plastic container to keep it sterile.
•     To open the plastic container, hold the short, wide end in one hand. Place your other hand on the longer portion of the container.
•     To break the seal, bend the larger end down and then up until broken (see Diagram 13).

Diagram 13



•     Once the seal has been broken, remove the short, wide end of the plastic container.
•     The needle will remain in the long part of the package.
•     While holding the needle and container in one hand, pick up the syringe and insert the syringe tip into the needle opening.
•     Attach the syringe to the needle by turning it clockwise until completely secured (see Diagram 14).

Diagram 14



•      Remove the needle cover by firmly pulling it straight off the syringe taking care not to touch the needle or allow the needle to touch any surfaces (see Diagram 15). Be careful not to bend or twist the cover during removal to avoid damage to the needle.

Diagram 15



•     While holding the syringe upright, remove any air bubbles by slowly pushing on the plunger until the air is removed (see Diagram 16).
Diagram 16


 g.    Choosing an injection site

•     The three recommended injection sites for Enbrel include: (1) the front of the middle thighs; (2) the abdomen, except for the 5 cm area right around the navel; and (3) the outer area of the upper arms (see Diagram 17). If you are self injecting, you should not use the outer area of the upper arms.

Diagram 17



•     A different site should be used for each new injection. Each new injection should be given at least 3 cm from an old site. Do NOT inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks. Avoid areas with scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
•     If you or the child have psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin patches (“psoriasis skin lesions”).


h.    Preparing the injection site and injecting the Enbrel solution

•     Wipe the site where Enbrel is to be injected with an alcohol swab, using a circular motion. Do NOT touch this area again before giving the injection.
•     When the cleaned area of skin has dried, pinch and hold it firmly with one hand. With the other hand, hold the syringe like a pencil.
•     With a quick, short motion, push the needle all the way into the skin at an angle between 45° and 90° (see Diagram 18). With experience, you will find the angle that is most comfortable for you or the child. Be careful not to push the needle into the skin too slowly, or with great force.
Diagram 18



•     When the needle is completely inserted into the skin, release the skin that you are holding. With your free hand, hold the syringe near its base to stabilise it. Then push the plunger to inject all of the solution at a slow, steady rate (see Diagram 19).

Diagram 19



•     When the syringe is empty, remove the needle from the skin; being careful to keep it at the same angle it was when it was inserted.
•     Press a cotton ball over the injection site for 10 seconds. Slight bleeding may occur. Do NOT rub the injection site. A bandage is optional.
 i.    Disposing of supplies

•     The syringe and needles should NEVER be re-used. Dispose of the needles and syringe as instructed by your doctor, nurse or pharmacist.

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Enbrel.