Pharmaceutical particulars : מידע רוקחי

6.      PHARMACEUTICAL PARTICULARS

6.1     List of excipients

Mannitol
Sucrose
L-arginine hydrochloride
Tris hydrochloride
Tromethamine (Tris base)
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
Chemical and physical in-use stability has been demonstrated for 16 hours at 2°C to 8°C in the primary packaging vial. If needed, the reconstituted solution once transferred into the IV bag can be stored for an additional eight hours at room temperature. From a microbiological point of view, once reconstituted, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

6.4     Special precautions for storage

Store in a refrigerator (2°C to 8°C).
Do not freeze.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
6.5     Nature and contents of container

W hite to off-white lyophilized powder/cake in a 20 mL vial (Type I glass) with a stopper (butyl rubber). Pack size of four or five vials.

6.6     Special precautions for disposal and other handling

Reconstitution
The following are needed before starting reconstitution:
• Calculated number of vials (see section 4.2).
• Same number of 20 mL (or larger) solvent syringes equipped with a 20 gauge (or larger) needle.
• Alcohol swabs.
• Large (50 mL or larger) sterile syringe. If a syringe pump is used for administration, multiple syringes should be used to contain the final volume of reconstituted product.
• Intravenous bags of polyolefin (PO) or polyvinyl chloride (PVC) material (150 mL or larger) to contain the final volume of reconstituted product (if administration is performed with IV bag).
• Water for injections.
• 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter.

Andexanet alfa does not need to be brought to room temperature before reconstitution or administration to the patient. Aseptic technique during the reconstitution procedure should be used.

Each vial is reconstituted according to the following instructions:
1. Remove the flip-top from each vial.
2. Wipe the rubber stopper of each vial with an alcohol swab.
3. Using a 20 mL (or larger) syringe and a 20 gauge (or larger) needle, withdraw 20 mL of water for injections.
4. Insert the syringe needle through the centre of the rubber stopper.
5. Push the plunger down to slowly inject the 20 mL of water for injections into the vial, directing the stream toward the inside wall of the vial to minimise foaming.

6. Gently swirl each vial, until all of the powder is completely dissolved. DO NOT SHAKE the vials, as this can lead to foaming. The dissolution time for each vial is approximately three to five minutes.
7. The reconstituted solution should be inspected for particulate matter and/or discolouration prior to administration. Do not use if opaque particles or discolouration are present.
8. For the most efficient reconstitution of the needed dose, and to minimise errors, inject each vial needed with 20 mL of water for injections before proceeding to the next step.
9. Use within eight hours after reconstitution when stored at room temperature.

Administration using a syringe pump
1. Once all required vials are reconstituted, the reconstituted solution is withdrawn from each vial, using the large volume (50 mL or larger) syringe equipped with a 20 gauge (or larger) needle.
2. The bolus and infusion are prepared in separate large volume syringes.
3. Due to the additional volume, the high dose bolus and infusion have to be further separated into additional syringes (two syringes apiece for bolus and infusion).
4. To prevent the inadvertent transfer of air, be careful to hold the syringe needle up,
and do not set the syringe down between multiple withdrawals from vials.
5. Attach ancillary equipment (i.e., extension tubing, 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter, syringe pump) in preparation for administration.
6. Administer the reconstituted solution at the appropriate rate.
7. Discard all used syringes, needles, and vials, including any unused portion of reconstituted solution.

Administration using intravenous bags
1. Once all required vials are reconstituted, withdraw the reconstituted solution from each vial, using the large volume (50 mL or larger) syringe equipped with a 20 gauge (or larger) needle.
2. Transfer the reconstituted solution from the syringe into an appropriate IV bag.
3. Repeat steps 1 and 2 as necessary to transfer the complete volume of the bolus and the infusion into a PO or PVC IV bags.
4. It is recommended that the bolus and infusion be split into two separate bags to ensure the correct administration rate. Although it is also permissible to use one PO or PVC IV bag for the bolus and infusion, the correct infusion rate must be ensured when switching from the bolus to the infusion.
5. Attach ancillary equipment (i.e., extension tubing, 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter, IV pump) in preparation for administration.
6. Administer the reconstituted solution at the appropriate rate.

Disposal
All used syringes, needles, and vials, including any unused portion of reconstituted solution, should be disposed of in accordance with local requirements.