Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Sucrose
Tromethamine
Sodium chloride
Polysorbate 80

6.2   Incompatibilities
In the absence of compatibility studies, 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 will be indicated on the packaging materials.

Reconstituted solution
BESPONSA contains no bacteriostatic preservatives. The reconstituted solution must be used immediately. If the reconstituted solution cannot be used immediately, it may be stored for up to 4 hours in a refrigerator (2 °C-8 °C). Protect from light and do not freeze.

Diluted solution

The diluted solution must be used immediately or stored at room temperature (20 °C-25 °C) or in a refrigerator (2 °C-8 °C). The maximum time from reconstitution through the end of administration should be ≤ 8 hours, with ≤ 4 hours between reconstitution and dilution. Protect from light and do not freeze.

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.
BESPONSA is a cytotoxic drug. Follow applicable special handling and disposal procedures.

For storage conditions after reconstitution and dilution, see section 6.3.

6.5       Nature and contents of container
Type I amber glass vial with chlorobutyl rubber stopper and crimp seal with flip- off cap containing 1 mg of powder.

Each carton contains 1 vial.

6.6       Special precautions for disposal and other handling
Instructions for reconstitution, dilution, and administration

Use appropriate aseptic technique for the reconstitution and dilution procedures. Inotuzumab ozogamicin (which has a density of 1.02 g/mL at 20°C) is light- sensitive and should be protected from ultraviolet light during reconstitution, dilution, and administration.

The maximum time from reconstitution through the end of administration should be ≤ 8 hours, with ≤ 4 hours between reconstitution and dilution.

Reconstitution

•    Calculate the dose (mg) and number of vials of BESPONSA required.
•    Reconstitute each 1 mg vial with 4 mL of water for injection, to obtain a single-use solution of 0.25 mg/mL of BESPONSA.
•    Gently swirl the vial to aid dissolution. Do not shake.


•   Inspect the reconstituted solution for particulates and discolouration. The reconstituted solution must be clear to slightly cloudy, colourless, and essentially free of visible foreign matter. If particles or discolouration are observed, do not use.
•   BESPONSA contains no bacteriostatic preservatives. The reconstituted solution must be used immediately. If the reconstituted solution cannot be used immediately, it may be stored in a refrigerator (2 °C-8 °C) for up to 4 hours. Protect from light and do not freeze.

Dilution

•   Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose according to patient body surface area. Withdraw this amount from the vial(s) using a syringe. Protect from light. Discard any unused reconstituted solution left in the vial.
•   Add the reconstituted solution to an infusion container with sodium chloride 9 mg/mL (0.9%) solution for injection, to a total nominal volume of 50 mL. The final concentration should be between 0.01 and 0.1 mg/mL. Protect from light. An infusion container made of polyvinyl chloride (PVC) (di(2-ethylhexyl)phthalate [DEHP]- or non-DEHP-containing), polyolefin (polypropylene and/or polyethylene), or ethylene vinyl acetate (EVA) is recommended.
•   Gently invert the infusion container to mix the diluted solution. Do not shake.
•   The diluted solution must be used immediately, stored at room temperature (20 °C-25 °C), or in a refrigerator (2 °C-8 °C). The maximum time from reconstitution through the end of administration should be ≤ 8 hours, with ≤ 4 hours between reconstitution and dilution.
Protect from light and do not freeze.

Administration

•   If the diluted solution is stored in a refrigerator (2 °C-8 °C), it must be allowed to equilibrate at room temperature (20 °C-25 °C) for approximately 1 hour prior to administration.
•   Filtration of the diluted solution is not required. However, if the diluted solution is filtered, polyethersulphone (PES)-, polyvinylidene fluoride (PVDF)-, or hydrophilic polysulphone (HPS)-based filters are recommended. Do not use filters made of nylon or mixed cellulose ester (MCE).
•   Protect the intravenous bag from light using an ultraviolet light-blocking cover (i.e., amber, dark brown, or green bags or aluminium foil) during infusion. The infusion line does not need to be protected from light.
•   Infuse the diluted solution for 1 hour at a rate of 50 mL/h at room temperature (20 °C-25 °C).
Protect from light. Infusion lines made of PVC (DEHP or non-DEHP-containing), polyolefin (polypropylene and/or polyethylene), or polybutadiene are recommended.

Do not mix BESPONSA or administer as an infusion with other medicinal products.

Table 8 shows the storage times and conditions for reconstitution, dilution, and administration of BESPONSA.

Table 8.    Storage times and conditions for reconstituted and diluted BESPONSA solution 
Maximum time from reconstitution through the end of administration ≤ 8 hoursa Reconstituted solution                              Diluted solution
After start of dilution              Administration
Use reconstituted solution     Use diluted solution              If the diluted solution is stored immediately or after being     immediately or after being        in a refrigerator (2 °C-8 °C), stored in a refrigerator       stored at room temperature        bring it to room temperature (2 °C-8 °C) for up to 4 hours. (20 °C-25 °C) or in a             (20 °C-25 °C) for Protect from light. Do not     refrigerator (2 °C-8 °C). The     approximately 1 hour prior to freeze.                        maximum time from                 administration. Administer Table 8.        Storage times and conditions for reconstituted and diluted BESPONSA solution 
Maximum time from reconstitution through the end of administration ≤ 8 hoursa Reconstituted solution                          Diluted solution
After start of dilution               Administration reconstitution through the end diluted solution as a 1-hour of administration should be       infusion at a rate of 50 mL/h at
≤ 8 hours, with ≤ 4 hours         room temperature between reconstitution and        (20 °C-25 °C). Protect from dilution. Protect from light. Do light.
not freeze.
a
With ≤ 4 hours between reconstitution and dilution.

Disposal

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