Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Sucrose
Polysorbate 20
Succinic acid
Sodium hydroxide

6.2   Incompatibilities
This medicinal product must not be mixed or diluted 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.
Reconstituted solution

From a microbiological point of view, the reconstituted solution 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 24 hours refrigerated (2 °C-8 °C), unless reconstitution has taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability of the reconstituted solution has been demonstrated for up to 72 hours refrigerated (2 °C-8 °C) and up to 24 hours at room temperature (9 °C-25 °C).

Diluted solution

From a microbiological point of view, the prepared solution for infusion 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 24 hours refrigerated (2 °C-8 °C), unless dilution has taken place in controlled and validated aseptic conditions. Chemical and physical stability of the prepared solution for infusion has been demonstrated for the durations listed in Table 7. The diluted solution must be discarded if storage time exceeds the limits specified in Table 7.

Table 7     Durations for which chemical and physical stability of the prepared solution for infusion have been demonstrated

Diluent used to prepare solution          Solution for infusion for infusion                              storage conditions1
Sodium chloride 9 mg/mL (0.9%)            Up to 72 hours refrigerated (2 °C  8 °C) or up to 4 hours at room temperature (9 °C  25 °C)
Sodium chloride 4.5 mg/mL (0.45%) Up to 72 hours refrigerated (2 °C  8 °C) or up to 8 hours at room temperature (9 °C  25 °C)
5% glucose                                Up to 72 hours refrigerated (2 °C  8 °C) or up to 8 hours at room temperature (9 °C  25 °C)
1
To ensure product stability, do not exceed specified storage durations.

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 and dilution of the medicinal product, see section 6.3.
6.5   Nature and contents of container

Polivy 30 mg powder for concentrate for solution for infusion:

6 mL vial (colourless Type 1 glass) closed with a stopper (fluororesin laminate), with an aluminium seal with plastic flip-off cap containing 30 mg polatuzumab vedotin. Pack size of one vial.


Polivy 140 mg powder for concentrate for solution for infusion:

20 mL vial (colourless Type 1 glass) closed with a stopper (fluororesin laminate), with an aluminium seal with plastic flip-off cap containing 140 mg polatuzumab vedotin. Pack size of one vial.

Not all pack sizes might be marketed
6.6    Special precautions for disposal and other handling

General precautions

Polivy contains a cytotoxic component. To be administered under the supervision of a physician experienced in the use of cytotoxic agents. Procedures for proper handling and disposal of antineoplastic and cytotoxic medicines should be used.

The reconstituted product contains no preservative and is intended for single-dose only. Proper aseptic technique throughout the handling of this medicinal product should be followed.

Polivy must be reconstituted using sterile water for injection and diluted into an intravenous infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection, or sodium chloride 4.5 mg/ml (0.45%) solution for injection, or 5% glucose prior to administration.

The reconstituted solution and solution for infusion should not be frozen or exposed to direct sunlight.

Instructions for reconstitution

•      Polivy 30 mg: Using a sterile syringe, slowly inject 1.8 mL of sterile water for injection into the 30 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab vedotin.
Direct the stream toward the wall of the vial and not directly on the lyophilized cake.
•      Polivy 140 mg: Using a sterile syringe, slowly inject 7.2 mL of sterile water for injection into the 140 mg Polivy vial to yield a single-dose solution containing 20 mg/mL polatuzumab vedotin. Direct the stream toward the wall of the vial and not directly on the lyophilized cake.
•      Swirl the vial gently until completely dissolved. Do not shake.
•      Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted solution should appear colourless to slightly brown, clear to slightly opalescent, and free of visible particulates. Do not use if the reconstituted solution is discoloured, is cloudy, or contains visible particulates.

Instructions for dilution

1.     Polivy must be diluted to a final concentration of 0.72-2.7 mg/mL in an intravenous infusion bag, with a minimum volume of 50 mL, containing 9 mg/mL sodium chloride solution for injection, or 4.5 mg/mL sodium chloride solution for injection, or 5% glucose.
2.     Determine the volume of 20 mg/mL reconstituted solution needed based on the required dose
(see below):
Polivy dose (mg/kg) X patient’s weight (kg)
Total Polivy dose (mL) to be further diluted =
Reconstituted vial concentration (20 mg/mL)
3.     Withdraw the required volume of reconstituted solution from the Polivy vial using a sterile syringe and dilute into the intravenous infusion bag. Discard any unused portion left in the vial.
4.     Gently mix the intravenous bag by slowly inverting the bag. Do not shake.
5.     Inspect the intravenous bag for particulates and discard if present.

Avoid transportation of the prepared solution for infusion as agitation stress can result in aggregation.
If the prepared infusion will be transported, remove air from the infusion bag and limit transportation to 30 minutes room temperature (9°C  25°C) or 24 hours refrigerated (2°C  8°C). If air is removed, an infusion set with a vented spike is required to ensure accurate dosing during the infusion. The total 
storage plus transportation times of the diluted product should not exceed the storage duration specified in Table 7 (see section 6.3).

Polivy must be administered using a dedicated infusion line equipped with sterile, non-pyrogenic, low-protein binding in-line or add-on filter (0.2 or 0.22 micrometer pore size) and catheter.

Polivy is compatible with intravenous infusion bags with product contacting materials of polyvinyl chloride (PVC) or polyolefins such as polyethylene (PE) and polypropylene. In addition, no incompatibilities have been observed with infusion sets or infusion aids with product contacting materials of PVC, PE, polyurethane, polybutadiene, acrylonitrile butadiene styrene, polycarbonate, polyetherurethane, fluorinated ethylene propylene, or polytetrafluorethylene and with filter membranes composed of polyether sulfone or polysulfone.

Disposal

Polivy is for single-use only.
Any unused product or waste material should be disposed of in accordance with local requirements.


7.    MARKETING AUTHORISATION HOLDER
Roche Pharmaceuticals (Israel) Ltd., P.O.Box 6391 Hod Hasharon 4524079.

8.    MARKETING AUTHORISATION NUMBER(S)

165-19-36153