Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Trehalose
D (-) -Mannitol
Di-sodium hydrogen phosphate
Citric acid monohydrate
Polysorbate 20
Water for injections

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

After opening

From a microbiological point of view, once opened, the medicinal product should be diluted and infused immediately.

After preparation of solution for infusion

Chemical and physical in-use stability has been demonstrated for 24 hours at 2 °C to 8 °C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4   Special precautions for storage

Store and transport refrigerated (2 °C – 8 °C).
Keep the vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
6.5   Nature and contents of container

Type I glass vial with a bromobutyl rubber stopper and an aluminium/plastic flip-off seal, containing 0.5 mL concentrate.

Pack size of 1 vial.

6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

General precautions

The solution for infusion should be prepared by a healthcare professional using proper aseptic technique throughout the handling of this medicinal product.

Use aseptic technique for dilution and preparation of dosing solutions.

Closed system transfer devices (CSTDs) must not be used for dose preparation of KIMMTRAK solution for infusion.

Parenteral medicinal products and infusion bags should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit.

Preparation

KIMMTRAK must be diluted prior to intravenous administration. Each vial of KIMMTRAK is intended for single-use only. Do NOT shake the KIMMTRAK vial.

Ensure the following supplies are available prior to preparing KIMMTRAK for administration:
•     1 mL sterile syringes with graduations of 2 decimal places.
•     Sterile needles.
•     Human albumin; use concentration as per local availability. Local concentrations include but not restricted to 4 % (40 g/L), 5 % (50 g/L), 20 % (200 g/L), 25 % (250 g/L).
•     A 100 mL infusion bag containing sodium chloride 9 mg/mL (0.9 %) solution for injection: o      The infusion bag should be constructed of polyolefins (PO) [such as polyethylene (PE) and polypropylene (PP)] or polyvinyl chloride (PVC).
•     A sterile, nonpyrogenic, low protein binding 0.2 micron in-line filter infusion set for administration of the final infusion bag.

Dilution and Administration

A 2-step process is required for preparation of the final KIMMTRAK dose: 
Step 1: Prepare the infusion bag

Using aseptic technique, prepare the infusion bag as follows: a.    Using a 1 mL syringe and a sterile needle, withdraw the calculated volume of human albumin into the syringe (see Table 6 below) and add to the 100 mL infusion bag containing sodium chloride 9 mg/mL (0.9 %) solution for injection to make a final human albumin concentration between 225 mcg/mL and 275 mcg/mL.

Table 6: Examples of human albumin concentration and acceptable withdrawal volumes Human albumin concentration     Acceptable volume range for addition to 100 mL infusion bag for human albumin concentration between 225 mcg/mL to 275 mcg/ mL
4 % (40 g/L)                     0.63 mL (0.57 mL to 0.69 mL)
5 % (50 g/L)                     0.50 mL (0.45 mL to 0.55 mL)
20 % (200 g/L)                    0.13 mL (0.12 mL to 0.14 mL)
25 % (250 g/L)                    0.10 mL (0.09 mL to 0.11 mL)
 b.    Gently homogenize the diluted solution by completing the following steps: i. Invert the infusion bag so that the entry port is positioned at the top of the bag and tap the side of port tubing to ensure that any residual solution is released into the bulk solution.
ii. Mix by gently rotating the bag lengthwise 360 degrees from the inverted position at least 5 times. Do NOT shake the infusion bag.
iii. Repeat (i) and (ii) an additional three times.

Step 2: Preparation of KIMMTRAK solution for infusion
 c.    Using a 1 mL syringe and a sterile needle, withdraw the required volume of KIMMTRAK 100 micrograms/ 0.5 mL as per the dose required (shown in Table 7 below) and add to the prepared 100 mL infusion bag containing sodium chloride 9 mg/mL (0.9 %) solution for injection, plus human albumin.
d.    Do NOT flush the needle and syringe on transfer. Discard the vial containing the unused portion of KIMMTRAK in accordance with local requirements. Do not prepare more than one dose from the vial.

Table 7: KIMMTRAK volumes required for addition to infusion bag
Day of treatment                  Dose (mcg) of              Volume (mL) of KIMMTRAK                    KIMMTRAK
Day 1                              20                        0.10
Day 8                              30                        0.15
Day 15 and weekly                        68                        0.34 thereafter e.    Mix the infusion bag by following the same procedure outlined in Step 1b.

Administration

•      Administer KIMMTRAK as intravenous infusion only.
•      Immediately administer the infusion over 15 to 20 minutes through a dedicated intravenous line.
A sterile, nonpyrogenic, low protein binding 0.2 micron in line filter infusion set should be used. Administer the entire contents of the KIMMTRAK infusion bag to the patient.
•      Upon completion of KIMMTRAK infusion, flush the infusion line with adequate volume of sterile sodium chloride 9 mg/mL (0.9 %) solution for injection, to ensure that the entire contents of the infusion bag are administered. Do not administer KIMMTRAK as an intravenous push or bolus. Do not mix KIMMTRAK with other drugs or administer other drugs through the same intravenous line.

Storage of prepared infusion bag

•      KIMMTRAK does not contain a preservative. The prepared infusion bag should be administered within 4 hours from the time of preparation including the duration of infusion.
During the 4 hour window, the KIMMTRAK infusion bag should remain below 30 °C.
•      If not used immediately, store the KIMMTRAK infusion bag in a refrigerator at 2 °C to 8 °C for up to 24 hours from the time of preparation which includes the time allowed for equilibration of the infusion bag to room temperature and the duration of the infusion.
•      Once removed from the refrigerator, KIMMTRAK infusion bag must not be refrigerated again.
Discard unused KIMMTRAK solution beyond the recommended storage time.