Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Glycine
Mannitol
Histidine
Histidine hydrochloride monohydrate
Polysorbate 80

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.
Reconstituted medicinal product

After reconstitution, chemical, physical, and microbiological in-use stability has been demonstrated for 24 hours at 2°C - 8°C.
From a microbiological point of view, the reconstituted 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.

Diluted medicinal product

After dilution, chemical, physical and microbiological in-use stability has been demonstrated between 0.5 mg/ml and 4 mg/ml for 24 hours at 2°C - 8°C, followed by 9 hours (including infusion time) at room temperature (up to 25°C). Use Aseptic Techniques.
From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C, followed by 9 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). Do not Freeze. Store in the original carton in order to protect from light.


For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
6.5     Nature and contents of container

100 mg of powder for concentrate for solution for infusion in a vial (type I glass) with a stopper (elastomeric rubber), seal (aluminium) and a flip off cap.

Each pack contains 1, 5, 10, or 25 vials.
Not all pack sizes may be marketed.

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

Reconstitution

Aseptic technique should be used during reconstitution.
1. The number of vials have to be determined to be reconstituted based on individual patient’s weight and the recommended dose of 20 mg/kg or 40 mg/kg.
Patient weight (kg) × dose (mg/kg) = patient dose (in mg). Patient dose (in mg) divided by 100 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, it should be rounded up to the next whole number.
Example: Patient weight (16 kg) × dose (20 mg/kg) = patient dose (320 mg). 320 mg divided by 100 mg/vial = 3.2 vials; therefore, 4 vials should be reconstituted.
Example: Patient weight (16 kg) × dose (40 mg/kg) = patient dose (640 mg).
640 mg divided by 100 mg/vial = 6.4 vials; therefore, 7 vials should be reconstituted.
2. The required number of vials needed for the infusion should be removed from the refrigerator and set aside for approximately 30 minutes to allow them to reach room temperature.
3. Each vial should be reconstituted by slowly injecting 10.0 ml of water for injections (WFI) to each vial. Each vial will yield 100 mg/10 ml (10 mg/ml). Forceful impact of the WFI on the powder and foaming should be avoided. This is performed by slow drop-wise addition of the WFI down the inside of the vial and not directly onto the lyophilised powder. Each vial should be tilted and rolled gently to dissolve the lyophilised powder. It should not be inverted, swirled, or shaken.
4. Immediate visual inspection should be performed on the reconstituted vials for particulate matter and discoloration. If upon immediate inspection particles are observed or if the solution is discoloured, the reconstituted medicinal product should not be used. The solution should be allowed to become dissolved.

Dilution

5. The reconstituted solution should be diluted in 5% glucose in water to a final concentration of 0.5 mg/ml to 4 mg/ml. See Table 6 for the recommended total infusion volume based on the patient weight.
6. The volume of reconstituted solution from each vial should be slowly withdrawn (calculated according to patient’s weight).
7. The reconstituted solution should be added slowly and directly into the 5% glucose solution.
Foaming or agitation of the infusion bag should be avoided. Air introduction into the infusion bag should be avoided.
8. To mix the infusion bag solution, gently invert or massage the infusion bag to mix. It should not be shaken.
9. To avoid administration of inadvertently introduced particles during dose IV preparation, it is recommended to use an in-line, low protein binding, 0.2 μm filter to administer Nexviazyme .
After the infusion is complete, the intravenous line should be flushed with glucose 5% in water.
10. Nexviazyme should not be infused in the same intravenous line with other medicinal products.


Table 6 – Projected intravenous infusion volumes for Nexviazyme administration by patient weight at 20 and 40 mg/kg Dose
Patient Weight Range        Total infusion volume for 20 mg/kg    Total infusion volume for 40 mg/kg (kg)                               (ml)                                  (ml) 1.25 to 5                             50                                    50 5.1 to 10                             50                                   100 10.1 to 20                            100                                   200 20.1 to 30                            150                                   300
30.1 to 35                            200                                   400 35.1 to 50                            250                                   500 50.1 to 60                            300                                   600 60.1 to 100                           500                                  1000 100.1 to 120                           600                                  1200 120.1 to 140                           700                                  1400 140.1 to 160                           800                                  1600 160.1 to 180                           900                                  1800 180.1 to 200                          1000                                  2000 
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.


7.    IMPORTER AND MARKETING AUTHORISATION HOLDER AND ITS ADDRESS
Sanofi Israel Ltd., Greenwork Park, P.O box 47, Yakum