Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Sucrose
L-methionine

Sodium phosphate monobasic monohydrate
Sodium phosphate dibasic heptahydrate
6.2   Incompatibilities

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

6.3   Shelf life

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

Reconstituted medicinal product

After reconstitution with sterile water for injection, chemical, physical and microbiological in-use stability has been demonstrated for up to 24 hours at 2-8°C or 12 hours at room temperature (up to 25°C).
From a microbiological point of view, the reconstituted medicinal product should be used immediately. If not used for dilution immediately, in-use storage times and conditions prior to dilution are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C or 12 hours at room temperature (up to 25°C).


Diluted medicinal product
After dilution with sodium chloride 9 mg/mL (0.9%) solution for injection, chemical, physical and microbiological in-use stability has been demonstrated between 0.1 mg/mL and 3.5 mg/mL for 24 hours at 2-8°C, and up to 12 hours (including infusion time) when stored at room temperature (up to 25°C).

From a microbiological point of view, the diluted medicinal product should be used immediately. If not used immediately after dilution, in-use storage times and conditions are the responsibility of the user and should normally not be longer than 24 hours at 2°C to 8°C followed by 12 hours (including infusion time) at room temperature (up to 25°C).

6.4   Special precautions for storage

Store in a refrigerator (2°C - 8°C).
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5   Nature and contents of container

20 mg of powder for concentrate for solution for infusion in a 20 mL vial (Type I glass) with a siliconized chlorobutyl-elastomer lyophilization stopper, and an aluminum seal with a plastic flip-off cap.

Each pack contains 1vial.

6.6   Special precautions for disposal and other handling
Vials are for single use only.

Infusions should be administered in a stepwise manner preferably using an infusion pump.

Preparation of the dosing solution

The powder for concentrate for solution for infusion must be reconstituted with sterile water for injection, diluted with sodium chloride 9 mg/mL (0.9%) solution for injection and then administered by intravenous infusion.
The reconstitution and dilution steps must be completed under aseptic conditions. Filtering devices should not be used at any time during the preparation of the infusion solution. Avoid foaming during reconstitution and dilution steps.

1)    Determine the number of vials to be reconstituted based on the individual patient’s weight and the prescribed dose.
Patient weight (kg) × dose (mg/kg) = patient dose (in mg). Patient dose (in mg) divided by       20 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, round up to the next whole number.
2)    Remove the required number of vials from refrigeration and set aside for approximately 20 to
30 minutes to allow them to reach room temperature.
3)    Reconstitute each vial by injecting:
5.1 mL of sterile water for injection into the 20 mg vial using a slow drop-wise addition technique to the inside wall of the vial.
4)    Tilt and roll each vial gently. Each vial will yield a 4 mg/mL clear, colorless solution.
5)    Visually inspect the reconstituted solution in the vials for particulate matter and discoloration.
Xenpozyme solution should be clear and colorless. Any vials exhibiting opaque particles or discoloration should not be used.
6)    Withdraw the volume of reconstituted solution, corresponding to the prescribed dose, from the appropriate number of vials and dilute with sodium chloride 9 mg/mL (0.9%) solution for injection, in a syringe or infusion bag depending on the volume of infusion (see Table 12 for the recommended total infusion volume based on patients age and/or weight).

Table 12: Recommended infusion volumes
Body weight        Body weight                     Body weight            Adult patients ≥3 kg to <10 kg    ≥10 kg to <20 kg                ≥20 kg (paediatric     (≥18 years) patients <18 years)
Dose          Total infusion          Total infusion         Total infusion        Total infusion (mg/kg)       volume (mL)             volume (mL)            volume (mL)           volume (mL) 0.03          Variable volume will Variable volume           5                     NA vary based on body      will vary based on weight                  body weight
0.1           Variable volume will 5                        10                     20 vary based on body weight
0.3           5                       10                    20                     100 0.6           10                      20                    50                     100 1             20                      50                    100                    100  2             50                      75                    200                    100
3             50                      100                   250                    100 •      For variable final volumes of infusion based on body weight in paediatric patients (see Table 12):
- Prepare an infusion solution at 0.1 mg/mL by adding 0.25 mL (1 mg) of the reconstituted solution prepared in step 3) and 9.75 mL of sodium chloride 9 mg/mL (0.9%) solution for injection in an empty 10 mL syringe.
- Calculate the volume (mL) required to obtain the patient dose (mg).
Example: 0.3 mg ÷ 0.1 mg/mL = 3 mL

•     Dilution instructions for 5 mL ≤ total volume ≤ 20 mL using a syringe: - Inject the required volume of the reconstituted solution slowly to the inside wall of the empty syringe.

- Add slowly the sufficient quantity of sodium chloride 9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid foaming within the syringe).

•     Dilution instructions for a total volume ≥ 50 mL using an infusion bag: - Empty infusion bag: o Inject slowly the required volume of the reconstituted solution from step 3) in the appropriate size sterile infusion bag.
o Add slowly the sufficient quantity of sodium chloride 9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid foaming within the bag).
- Pre-filled infusion bag: o Withdraw from the infusion bag pre-filled with sodium chloride 9 mg/mL (0.9%) solution for injection the volume of normal saline to obtain a final volume as specified in Table 12.
o Add slowly the required volume of the reconstituted solution from step 3) into the infusion bag (avoid foaming within the bag).

7)       Gently invert the syringe or the infusion bag to mix. Do not shake. Because this is a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after dilution.
8)       The diluted solution must be filtered through an in-line low protein-binding 0.2 μm filter during administration.
9)       After the infusion is complete, the infusion line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection using the same infusion rate as the one used for the last part of the infusion.

Disposal

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