Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany
Ronapreve is indicated for:
The use of Ronapreve should take into account information on the activity of Ronapreve against viral variants of concern. See sections 4.4 and 5.1.
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.
The dosage in patients who do not require supplemental oxygen is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection (see Tables 1 and 3). See sections 4.4 and 5.1. For these patients only, casirivimab with imdevimab should be given within 7 days of the onset of symptoms of COVID-19.
The dosage in patients who require supplemental oxygen (including low flow and high flow oxygen devices, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)) is 4 000 mg of casirivimab and 4 000 mg of imdevimab administered as a single intravenous infusion (see Table 2 of Ronapreve SmPC 120 mg/mL + 120 mg/mL). See section 5.1.
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 3).
Casirivimab with imdevimab should be given as soon as possible after contact with a case of COVID-19.
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 3). 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).
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.
No dosage adjustment is required (see section 5.2).
No dosage adjustment is required (see section 5.2).
No dosage adjustment is required (see section 5.2).
The safety and efficacy of casirivimab and imdevimab in children < 12 years of age has not yet been established. No data are available.
Ronapreve is for intravenous or subcutaneous use only.
For detailed instructions on the preparation and administration of Ronapreve, see section 6.6.
Table 1. Recommended dilution and intravenous infusion instructions for 600 mg casirivimab and 600 mg imdevimab or 300 mg casirivimab and 300 mg imdevimab:
| Indication | Size of prefilled 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) dextrose infusion bag | Ronapreve Dose | Total Volume for 1 Dose | Volume to be withdrawn from each respective vial and injected into a single prefilled 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) dextrose infusion bag of 50- 250 mL for co-administration | Minimum Infusion Time |
| Treatment (patients not on supplemental oxygen), Postexposure prophylaxis (single dose), Pre- exposure prophylaxis (initial dose) | 50 mL, 100 mL, 150 mL | 600 mg casirivimab and 600 mg imdevimab | 10 mL | 2.5 mL from two 300 mg single-use vials of casirivimab 2.5 mL from two 300 mg single-use vials of imdevimab | 20 minutes |
| 250 mL | 30 minutes | ||||
| Pre-exposure prophylaxis (repeat dose) | 50 mL, 100 mL, 150 mL | 300 mg casirivimab and 300 mg imdevimab | 5 mL | 2.5 mL from one 300 mg single-use vial of casirivimab 2.5 mL from one 300 mg single-use vial of imdevimab | 20 minutes |
| 250 mL | 30 minutes |
Table 2. Recommended dilution and intravenous infusion instructions for 4 000 mg casirivimab and 4 000 mg imdevimab:
| Indication | Size of prefilled 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) dextrose infusion bag | Ronapreve Dose | Total Volume for 1 Dose | Volume to be withdrawn from each respective vial and injected into a single prefilled 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) dextrose infusion bag of 50- 250 mL for co-administration | Minimum Infusion Time |
| Treatment (patients on supplemental oxygen) | 250 mL* | 4 000 mg casirivimab and 4 000 mg imdevimab | 66.6 mL | 33.3 mL total of casirivimab from the 300 mg single-use vials 33.3 mL total of imdevimab from the 300 mg single-use vials Also refer to Ronapreve SmPC 120 mg/mL + 120 mg/mL | 60 minutes |
* Withdraw and discard 66.6 mL of 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) dextrose from the infusion bag prior to adding casirivimab and imdevimab
The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse reactions (see section 4.4).
For detailed instructions on the preparation and administration of Ronapreve, see section 6.6.
Subcutaneous injections of casirivimab and imdevimab should be made consecutively at separate body sites (into upper thighs, upper outer arms or abdomen, avoiding 5 cm around the navel and the waistline).
Table 3. Preparation of 600 mg casirivimab and 600 mg imdevimab or 300 mg casirivimab and 300 mg imdevimab for subcutaneous injection:
| Indication | Ronapreve Dose | Total Volume for 1 Dose | Volume to be withdrawn from each respective vial to prepare 4 syringes |
| Treatment (patients not on supplemental oxygen), Post- exposure prophylaxis (single dose), Pre- exposure prophylaxis (initial dose) | 600 mg casirivimab and 600 mg imdevimab | 10 mL | 2.5 mL from two 300 mg single-use vials of casirivimab 2.5 mL from two 300 mg single-use vials of imdevimab |
| Indication | Ronapreve Dose | Total Volume for 1 Dose | Volume to be withdrawn from each respective vial to prepare 2 syringes |
| Pre-exposure prophylaxis (repeat dose) | 300 mg casirivimab and 300 mg imdevimab | 5 mL | 2.5 mL from one 300 mg single-use vial of casirivimab 2.5 mL from one 300 mg single-use vial of imdevimab |
Doses up to 4 000 mg each of casirivimab and imdevimab have been administered in clinical trials. No data are available beyond this dose.
There is no known specific antidote for casirivimab and imdevimab overdose. Treatment of overdose should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
Unopened vial: 2 years.
Co-packaged 300 mg single-use vials:
After initial puncture: the medicinal product should be used immediately, any remaining product should be discarded.
Diluted solution for intravenous administration:
Solution in vial requires dilution prior to administration. The prepared infusion solution is intended to be used immediately. The chemical and physical in-use stability data has been demonstrated for 20 hours at room temperature (up to 25°C) and 72 hours at 2°C to 8°C. From a microbiological point of view, the prepared infusion solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions. If refrigerated, allow the intravenous infusion bag to equilibrate to room temperature for approximately 30 minutes prior to administration.
Storage of syringes for subcutaneous administration:
The prepared syringes should be administered immediately. The chemical and physical in-use stability data has been demonstrated for 24 hours at room temperature (up to 25°C) and 72 hours at 2°C to 8°C. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless preparation has taken place in controlled and validated aseptic conditions. If refrigerated, allow the syringes to equilibrate to room temperature for approximately 10-15 minutes prior to administration.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Do not shake.
Keep the vials in the original carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
Ronapreve is provided in 6 mL clear Type 1 glass vials.
Ronapreve 300 mg + 300 mg solution for injection/infusion, single-use vials:
Each carton contains 1 vial of each antibody:
Pack of two 6 mL clear Type I glass vials with butyl rubber stopper containing one vial of 2.5 mL solution of 300 mg of casirivimab and one vial of 2.5 mL solution of 300 mg of imdevimab.
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.
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.
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 9 mg/mL (0.9%) sodium chloride injection or 50 mg/mL (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 9 mg/mL (0.9%) sodium chloride injection or 50 mg/mL (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.
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 3). 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 3) 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 2ºC to 8ºC for no more than 72 hours and at room temperature up to 25ºC for no more than 24 hours. If refrigerated, allow the syringes to equilibrate to room temperature for approximately 10-15 minutes prior to administration.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
The following points should be strictly adhered to regarding the use and disposal of syringes and other medicinal sharps:
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