Posology and method of administration

Administration should be under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible. Individuals should be monitored after administration according to local medical practice.

Posology

Treatment

The dosage in adult patients and in adolescent patients 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection (see Table 1). See sections 4.4 and 5.1.

Casirivimab with imdevimab should be given within 7 days of the onset of symptoms of COVID-19.

Prevention

Post-exposure prophylaxis

The dosage in adult patients and in adolescent patients 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection (see Tables 1 and 2).

Casirivimab with imdevimab should be given as soon as possible after contact with a case of COVID-19.

Pre-exposure prophylaxis

The initial dose in adult patients and in adolescent patients 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection (see Tables 1 and 2). Subsequent doses of 300 mg of casirivimab and 300 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection may be given every 4 weeks until prophylaxis is no longer required. There are no data on repeat dosing beyond 24 weeks (6 doses).

Missed dose

In case of repeated dosing for pre-exposure prophylaxis, if a dose of Ronapreve is missed it should be administered as soon as possible. Thereafter, the schedule of administration should be adjusted to maintain the appropriate interval between doses.

Special populations

• Elderly - No dosage adjustment is required (see section 5.2 SmPC).
  
• Renal impairment - No dosage adjustment is required (see section 5.2 SmPC). 
  
• Hepatic impairment - No dosage adjustment is required (see section 5.2 SmPC).
  
• Paediatric population - The safety and efficacy of casirivimab and imdevimab in children < 12 years of age has not yet been established. No data are available.

Preparation

Preparation of Ronapreve for intravenous infusion

Ronapreve should be prepared by a healthcare professional using aseptic technique:

1. Remove the casirivimab and imdevimab vials from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation.

-  Do not expose to direct heat.

-  Do not shake the vials.

2. Inspect casirivimab and imdevimab vials visually for particulate matter and discolouration prior to administration. Should either be observed, the vial must be discarded and replaced with a new vial.

-  The solution for each vial should be clear to slightly opalescent, colourless to pale yellow.

3. Obtain a prefilled intravenous infusion bag [made from polyvinyl chloride (PVC) or polyolefin (PO)] containing either 50 mL, 100 mL, 150 mL, or 250 mL of 0.9% sodium chloride injection or 5% dextrose injection.
4. Using a sterile syringe and needle, withdraw the appropriate volume of casirivimab and imdevimab from each respective vial and inject into a prefilled infusion bag containing 0.9% sodium chloride injection or 5% dextrose injection (see section 4.2, Table 1).
5. Gently mix infusion bag by inversion. Do not shake.
6. Ronapreve is preservative‑free and therefore, the diluted infusion solution should be administered immediately.

Administration of Ronapreve by intravenous infusion

• Gather the recommended materials for infusion:
  • Polyvinyl chloride (PVC), polyethylene (PE)‑lined PVC, or polyurethane (PU) infusion set
  • In-line or add-on 0.2 μm to 5 μm polyethersulfone, polysulfone, or polyamide filter for intravenous administration.
• Attach the infusion set to the intravenous bag.
• Prime the infusion set.
• Administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2 μm to 5 μm polyethersulfone, polysulfone, or polyamide filter for intravenous administration.
• The prepared infusion solution should not be administered simultaneously with any other medicinal product. The compatibility of casirivimab and imdevimab injection with intravenous solutions and medicinal products other than 0.9% sodium chloride injection or 5% dextrose injection is not known.
• After infusion is complete, flush the tubing with 0.9% sodium chloride injection or 5% dextrose injection to ensure delivery of the required dose.
•  Individuals should be monitored post intravenous infusion according to local medical practice.

Preparation of Ronapreve for subcutaneous injection

Remove the casirivimab and imdevimab vial(s) from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation.

Do not expose to direct heat.

Do not shake the vials.

Inspect casirivimab and imdevimab vial(s) visually for particulate matter and discolouration prior to administration. Should either be observed, the vial must be discarded and replaced with a new vial. The solution for each vial should be clear to slightly opalescent, colourless to pale yellow.

1. Ronapreve should be prepared using the appropriate number of syringes (see section 4.2, Table 2). Obtain 3 mL or 5 mL polypropylene syringes with luer connection and 21-gauge transfer needles.
2. Using a sterile needle and syringe, withdraw the appropriate volume of casirivimab and imdevimab from each respective vial into each syringe (see section 4.2, Table 2) for a total of 4 syringes for the 1 200 mg combined total dose and a total of 2 syringes for the 600 mg combined total dose. Store any remaining product as directed in Section 6.3.
3. Replace the 21-gauge transfer needle with a 25-gauge or 27-gauge needle for subcutaneous injection.
4. This product is preservative-free and therefore, the prepared syringes should be administered immediately. If immediate administration is not possible, store the prepared casirivimab and imdevimab syringes at 2 ºC to 8 ºC for no more than 72 hours and at room temperature up to 25 ºC for no more than 24 hours. If refrigerated, allow the syringes to equilibrate to room temperature for approximately 10-15 minutes prior to administration.

Administration of Ronapreve by subcutaneous injection

• For the administration of Ronapreve 1 200 mg dose (600 mg of casirivimab and 600 mg of imdevimab), gather 4 syringes (see section 4.2, Table 2) and prepare for subcutaneous injections.
• For the administration of Ronapreve 600 mg dose (300 mg of casirivimab and 300 mg of imdevimab), gather 2 syringes (see section 4.2, Table 2) and prepare for subcutaneous injections.
• Due to the volume, administer the subcutaneous injections consecutively, at separate body sites (into upper thighs, upper outer arms, or abdomen, avoiding 5 cm around the navel and the waistline).

Method of administration

Ronapreve is for intravenous or subcutaneous use only.

Table 1:  Recommended dilution instructions for Ronapreve (casirivimab and imdevimab) for intravenous infusion