Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Betadex sulfobutyl ether sodium
Hydrochloric acid (to adjust pH) (E507)
Sodium hydroxide (to adjust pH) (E524)

6.2   Incompatibilities
This medicinal product must not be mixed or administered simultaneously with other medicinal products in the same dedicated line except those mentioned in section 6.6.

6.3   Shelf life

Unopened vials
The expiry date of the product is indicated on the packaging materials.
Reconstituted and diluted solution for infusion
After reconstitution dilute immediately.

Store diluted remdesivir solution for infusion up to 24 hours at room temperature (20°C to 25°C) or 48 hours in a refrigerator (2°C – 8°C). Dilute within the same day as administration.

6.4   Special precautions for storage

No special storage conditions are required. It is recommended to store the medicinal product at room temperature.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5   Nature and contents of container

Type I clear glass vial, an elastomeric closure, and an aluminium overseal with a flip-off cap.

Pack size: 1 vial

6.6     Special precautions for disposal and other handling
Prepare solution for infusion under aseptic conditions and on the same day as administration. Remdesivir should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. Should either be observed, the solution should be discarded and fresh solution prepared.

Remdesivir must be reconstituted with 19 mL sterile water for injections and diluted in sodium chloride 9 mg/mL (0.9%) solution for injection before being administered via intravenous infusion over 30 to 120 minutes.

Preparation of remdesivir solution for infusion

Reconstitution
Remove the required number of single-use vial(s) from storage. For each vial:
•    Aseptically reconstitute remdesivir powder for concentrate for solution for infusion by addition of 19 mL of sterile water for injections using a suitably sized syringe and needle per vial, and insert the needle in the centre of the vial stopper.
◦       Discard the vial if a vacuum does not pull the sterile water for injections into the vial.
•    Only use sterile water for injection to reconstitute remdesivir powder.
•    Immediately shake the vial for 30 seconds.
•    Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
•    If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
•    Inspect the vial to ensure the container closure is free from defects and the solution is free of particulate matter.
•    Dilute immediately after reconstitution.

Dilution
Care should be taken to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is recommended to administer immediately after preparation when possible.

Adults and paediatric patients (weighing at least 40 kg)
•     Using Table 10, determine the volume of sodium chloride 9 mg/mL (0.9%) solution for injection to withdraw from the infusion bag.

Table 10:        Recommended dilution instructions – Reconstituted remdesivir powder for concentrate for solution for infusion
Sodium chloride      Volume to be withdrawn and
Remdesivir     9 mg/mL (0.9%) infusion discarded from sodium chloride                     Required volume of dose          bag volume to be used  9 mg/mL (0.9%) infusion bag                     reconstituted remdesivir 200 mg                 250 mL                      40 mL                                      2 × 20 mL
(2 vials)              100 mL                      40 mL                                      2 × 20 mL 100 mg                 250 mL                      20 mL                                        20 mL (1 vial)              100 mL                      20 mL                                        20 mL NOTE: 100 mL should be reserved for patients with severe fluid restriction, e.g. with ARDS or renal failure.

•       Withdraw and discard the required volume of sodium chloride 9 mg/mL from the bag using an appropriately sized syringe and needle per Table 10.
•       Withdraw the required volume of reconstituted remdesivir using an appropriately sized syringe per Table 10. Discard any unused portion remaining in the remdesivir vial.
•       Transfer the required volume of reconstituted remdesivir to the selected infusion bag.

•     Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
•     The prepared solution is stable for 24 hours at room temperature (20°C to 25°C) or 48 hours in the refrigerator (2°C to 8°C).

Paediatric patients (at least 4 weeks of age and weighing 3 kg to less than 40 kg)
•    Further dilute the 100 mg/20 mL (5 mg/mL) remdesivir concentrate to a fixed concentration of 1.25 mg/mL using 0.9% sodium chloride.
•    The total required infusion volume of the 1.25 mg/mL remdesivir solution for infusion is calculated from the paediatric weight-based dosing regimens of 5 mg/kg for the Loading Dose and 2.5 mg/kg for each Maintenance Dose.
•    Small 0.9% sodium chloride infusion bags (e.g., 25, 50, or 100 mL) or an appropriately sized syringe should be used for paediatric dosing. The recommended dose is administered via IV infusion in a total volume dependent on the dose to yield the target remdesivir concentration of 1.25 mg/mL.
•    A syringe may be used for delivering volumes <50 mL.

After infusion is complete, flush with at least 30 mL of sodium chloride 9 mg/mL.

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