VEKLURY Powder for concentrate for solution for infusion Ref.[27515] Active ingredients: Remdesivir

Patients should be monitored when receiving remdesivir (see section 4.4).

Patients receiving remdesivir in an outpatient setting should be monitored according to local medical practice. Use under conditions where treatment of severe hypersensitivity reactions, including anaphylaxis, is possible.

Posology

Table 1. Recommended dose in adults and paediatric patients:

Table 2. Treatment duration:

Special populations

Elderly

No dose adjustment of remdesivir is required in patients over the age of 65 years (see sections 5.1 and 5.2).

Renal impairment

No dose adjustment of remdesivir is required in patients with renal impairment, including those on dialysis. However, safety data in patients with severe renal impairment and end stage renal disease (ESRD) are limited (see section 4.4) and based on a 5-day treatment duration. The timing of administration of remdesivir is without regard to dialysis (see section 5.2).

Hepatic impairment

No dose adjustment of remdesivir is required in patients with mild, moderate and severe hepatic impairment (Child-Pugh Class A, B, C) (see section 5.2). However, safety data in patients with severe hepatic impairment are limited and only based on a single 100 mg dose administration.

Paediatric population

The safety and efficacy of remdesivir in children less than 4 weeks of age and weighing less than 3 kg have not yet been established. No data are available.

Immunocompromised population

The safety and efficacy of remdesivir in immunocompromised patients have not yet been established. Only limited data are available (see section 4.4).

Method of administration

For intravenous use.

Remdesivir is for administration by intravenous infusion after reconstitution and further dilution.

It must not be given as an intramuscular (IM) injection.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

Table 3. Recommended rate of infusion – for reconstituted and diluted remdesivir powder for concentrate for solution for infusion in adults and paediatric patients weighing at least 40 kg:

Table 4. Recommended rate of infusion – for reconstituted and diluted remdesivir powder for concentrate for solution for infusion in paediatric patients at least 4 weeks of age and weighing at least 3 kg but less than 40 kg:

^a Rate of infusion may be adjusted based on total volume to be infused.

Treatment of overdose with remdesivir should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with remdesivir.

Unopened vials: 4 years.

Reconstituted and diluted solution for infusion: Store diluted remdesivir solution for infusion up to 24 hours at below 25°C or 48 hours in a refrigerator (2°C – 8°C).

No special precautions for storage.

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

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

Pack size: 1 vial.

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 12, determine the volume of sodium chloride 9 mg/mL (0.9%) solution for injection to withdraw from the infusion bag.

Table 12. Recommended dilution instructions – Reconstituted remdesivir powder for concentrate for solution for infusion:

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 12.
• Withdraw the required volume of reconstituted remdesivir using an appropriately sized syringe per Table 12. 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.