Pharmaceutical particulars : מידע רוקחי

6.      PHARMACEUTICAL PARTICULARS
6.1     List of excipients

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
1,2-Dioleoyl-sn-glycero-3-phospho-L-serine monosodium salt (OOPS)

6.2     Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3     Shelf life

Unopened vial of powder
The expiry date of the product is indicated on the packaging materials.

Reconstituted suspension

Chemical and physical stability has been demonstrated for 6 hours up to 25º C.
From a microbiological point of view, immediate use is recommended.
If not used immediately, the reconstituted, filtered and diluted solution in-use storage times and conditions prior to use of the reconstituted product must not be longer than 6 hours at 25º C.
Do not refrigerate or freeze the solution.

6.4     Special precautions for storage

Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the 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

50 mL type I glass vial with a grey butyl rubber stopper, aluminium seal and plastic flip-off cap, containing 4 mg of mifamurtide.

Each carton contains 1 vial and 1 single-use, non-pyrogenic, sterile filter for MEPACT supplied in a PVC-grade blister.

6.6     Special precautions for disposal and other handling

MEPACT must be reconstituted, filtered using the filter provided and further diluted using aseptic technique, prior to administration.

Each vial should be reconstituted with 50 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. After reconstitution, each mL suspension in the vial contains 0.08 mg mifamurtide. The volume of reconstituted suspension corresponding to the calculated dose is extracted through the filter provided and further diluted with additional 50 mL sodium chloride 9 mg/mL (0.9%) solution for injection according to the detailed instructions shown below.

The reconstituted, filtered and diluted suspension for infusion is a homogenous, white to off-white, opaque liposomal suspension, free of visible particles and free of foam and lipid lumps.

Instructions for preparation of MEPACT for intravenous infusion

Materials provided in each package:
•    MEPACT powder for concentrate for dispersion for infusion (vial)
•    Filter for MEPACT 
Materials required but not provided:
•    Sodium chloride 9 mg/mL (0.9%) solution for injection, 100 mL bag
•    1 single use 60 or 100 mL sterile syringe with luer lock
•    2 medium (18) gauge sterile injection needles 
It is recommended that the reconstitution of the liposomal suspension should be performed in a laminar flow cabinet utilising sterile gloves using aseptic technique.

The lyophilised powder should be allowed to reach a temperature between approximately 20 °C-25 °C prior to reconstitution, filtering using the filter provided and dilution. This should take approximately 30 minutes.

1.    The cap of the vial should be removed and the stopper cleaned using an alcohol pad.
2.    The filter should be removed from the blister pack, and the cap removed from the filter spike. The spike should then be inserted into the vial septum firmly until seated. The filter luer connector cap should not be removed at this time.
3.    The 100 mL sodium chloride 9 mg/mL (0.9%) solution for injection bag, needle and syringe should be unpacked (not provided in the pack).
4.    The site of the sodium chloride 9 mg/mL (0.9%) solution for injection bag where the needle is going to be inserted should be swabbed with an alcohol pad.
5.    Using the needle and syringe, 50 mL of sodium chloride 9 mg/mL (0.9%) solution for injection should be withdrawn from the bag.
6.    After removing the needle from the syringe, the syringe should be attached to the filter by opening the filter luer connector cap (figure 1).


Figure 1

7.    The sodium chloride 9 mg/mL (0.9%) solution for injection is added to the vial by slow, firm depression of the syringe plunger. The filter and syringe must not be removed from the vial.
8.    The vial should be allowed to stand undisturbed for 1 minute to ensure thorough hydration of the dry substance.
9.    The vial should then be shaken vigorously for 1 minute while keeping the filter and syringe attached. During this time the liposomes are formed spontaneously (figure 2).



Figure 2

10.   The desired dose may be withdrawn from the vial by inverting the vial and slowly pulling back on the syringe plunger (figure 3). Each mL reconstituted suspension contains 0.08 mg mifamurtide. The volume of suspension to be withdrawn for dose quantities is calculated as follows:

Volume to withdraw = [12.5 x calculated dose (mg)] mL

For convenience, the following table of concordance is provided:
Dose                       Volume
1.0 mg                      12.5 mL
2.0 mg                       25 mL
3.0 mg                      37.5 mL
4.0 mg                       50 mL


Figure 3
11.   The syringe should then be removed from the filter and a new needle placed on the suspension-filled syringe. The bag injection site should be wiped with an alcohol pad and the suspension in the syringe should be injected into the original bag containing the remaining 50 mL of sodium chloride 9 mg/mL (0.9%) solution for injection (figure 4).



Figure 4

12.   The bag should be gently swirled to mix the solution.
13.   Patient identification, time and date should be added to the label on the bag containing the reconstituted, filtered and diluted liposomal suspension.
14.   Chemical and physical in-use stability has been demonstrated for 6 hours at room temperature (between approximately 20 °C-25 °C).
15.   From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 6 hours at room temperature.
16.   Based on the liposomal nature of the product, use of an infusion set with an in-line filter during administration is not recommended.
17.   The liposomal suspension is infused intravenously over about 1 hour.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.