Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom
Ronapreve is indicated for the prophylaxis and treatment of acute Covid-19 infection (see sections 4.2, 4.6 4.8, 5.1 and 5.2 for additional information on extent and limits of accepted clinical trial evidence).
Preparation and administration of Ronapreve should be initiated and monitored by a qualified healthcare provider using aseptic technique. Administration should be under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible. Individuals should be monitored post intravenous infusion according to local medical practice.
Casirivimab and imdevimab must be administered together, after dilution, as a single intravenous (IV) infusion.
Casirivimab and imdevimab must be administered consecutively by subcutaneous injection.
The dosage is 600 mg of casirivimab and 600 mg of imdevimab administered either together as a single IV infusion via pump or gravity (see Table 1) or by subcutaneous injection (see Table 3).
Casirivimab with imdevimab should be given together as soon as possible after a positive viral test for SARS-CoV-2.
The dosage is 600 mg of casirivimab and 600 mg of imdevimab administered together either as a single IV infusion via pump or gravity (see Table 1) or by subcutaneous injection (see Table 3).
Casirivimab and imdevimab should be given concurrently as soon as possible following exposure to SARS-CoV-2.
For individuals who require repeat dosing for ongoing prevention, i.e. those who have a medical condition making them unlikely to respond to or be protected by vaccination:
The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse events (see section 4.8).
Doses should not be missed and the dosing regimen should be adhered to as closely as possible. If a dose of Ronapreve is missed it should be administered as soon as possible. The schedule of administration should be adjusted to maintain the appropriate interval between doses.
No dosage adjustment is required in individuals with mild or moderate renal impairment, or in patients with creatinine clearance (CrCl) < 15 mL/min including those on dialysis. Limited data are available in individuals with severe renal impairment (see section 5.2).
No dosage adjustment is required in individuals with mild hepatic impairment. Limited data are available in individuals with moderate hepatic impairment. Casirivimab and imdevimab have not been studied in individuals with severe hepatic impairment (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. No dosage adjustment is recommended in paediatric individuals ≥12 years of age and older and weighing ≥ 40 kg (see section 5.2).
Ronapreve is for intravenous infusion or subcutaneous injection only.
For detailed instructions on the preparation and administration of Ronapreve, see section 6.6.
Table 1. Recommended Dilution Instructions for Ronapreve (casirivimab and imdevimab) for IV Infusion:
| Indication | Ronapreve Dose (Total) | Total Volume for 1 Dose | Volume to be withdrawn from each respective vial and inject into a prefilled 0.9% sodium chloride or 5% dextrose infusion bag |
|---|---|---|---|
| Treatment and Prevention – single dose | 600 mg casirivimab and 600 mg imdevimab (1.200 mg dose) | 10 mL | 2.5 mL from two 6 mL single -use vials of casirivimab 2.5 mL from two 6 mL single-use vial of imdevimab |
| 5.0 mL from one 20 mL multidose vial of casirivimab 5.0 mL from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL from two 6 mL single-use vials of casirivimab 5.0 mL from one 20 mL multidose vial of imdevimab | |||
| 5.0 mL from one 20 mL multidose vial of casirivimab 2.5 mL from two 6 mL single-use vials of imdevimab | |||
| Prevention – repeat dose | 300 mg casirivimab and 300 mg imdevimab (600 mg dose) | 5 mL | 2.5 mL from one 6 mL single-use vial of casirivimab 2.5 mL from one 6 mL single-use vial of imdevimab |
| 2.5 mL from one 20 mL multidose vial of casirivimab 2.5 mL from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL from one 6 mL single-use vial of casirivimab 2.5 mL from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL from one 20 mL multidose vial of casirivimab 2.5 mL from one 6 mL single-use vial of imdevimab |
Table 2. Minimum Infusion Time for IV Infusion Bag Volumes for diluted Ronapreve 600 mg of casirivimab and 600 mg of imdevimab (1.200 mg dose) or 300 mg of casirivimab and 300 mg of imdevimab (600 mg dose):
| Size of Prefilled 0.9% Sodium Chloride or 5% Dextrose Infusion Bag | Minimum Infusion Time Ronapreve 600 mg casirivimab and 600 mg imdevimab (1.200 mg) | Minimum Infusion Time Ronapreve 300 mg casirivimab and 300 mg imdevimab (600 mg) |
|---|---|---|
| 50 mL | 20 minutes | 20 minutes |
| 100 mL | 20 minutes | 20 minutes |
| 150 mL | 20 minutes | 20 minutes |
| 250 mL | 30 minutes | 30 minutes |
The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse events.
For detailed instructions on the preparation and administration of Ronapreve, see section 6.6.
Administer the subcutaneous injections concurrently each at a different injection site: the upper thighs, the upper outer arms, or the abdomen, except for 5 cm around the navel. The waistline should be avoided.
When administering the subcutaneous injections, it is recommended that healthcare professionals use different quadrants of the abdomen or upper thighs or upper outer arms to space apart each 2.5 mL subcutaneous injection of casirivimab and imdevimab (see section 4.8).
Ronapreve subcutaneous injections should not be administered into areas where the skin is tender, damaged, bruised, or scarred.
Table 3. Preparation of Ronapreve (casirivimab and imdevimab) for Subcutaneous Injection:
| Indication | Ronapreve Dose (Total) | Total Volume for 1 Dose | Volume to be withdrawn to prepare 4 syringes |
|---|---|---|---|
| Treatment and Prevention – single dose | 600 mg casirivimab and 600 mg imdevimab (1.200 mg dose) | 10 mL | 2.5 mL from two 6 mL single-use vials of casirivimab 2.5 mL from two 6 mL single-use vials of imdevimab |
| 2.5 mL (2x) from one-20 mL multidose vial of casirivimab 2.5 mL (2x) from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL from two 6 mL single-use vials of casirivimab 2.5 mL (2x) from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL (2x) from one 20 mL multidose vial of casirivimab 2.5 mL from two 6 mL single-use vials of imdevimab | |||
| Prevention – repeat dose | 300 mg casirivimab and 300 mg imdevimab (600 mg dose) | 5 mL | 2.5 mL from one 6 mL single-use vial of casirivimab 2.5 mL from one 6 mL single-use vial of imdevimab |
| 2.5 mL from one 20 mL multidose vial of casirivimab 2.5 mL from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL from one 6 mL single-use vial of casirivimab 2.5 mL from one 20 mL multidose vial of imdevimab | |||
| 2.5 mL from one 20 mL multidose vial of casirivimab 2.5 mL from one 6 mL single-use vial of imdevimab |
Doses up to 8,000 mg (4,000 mg each of casirivimab and imdevimab, approximately 7-times the recommended dose) have been administered in clinical trials with no new safety concerns identified.
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: 12 months.
After initial puncture: If not used immediately, the product in the vial can be stored for 6 hours at room temperature up to 25°C or for no more than 24 hours refrigerated between 2°C to 8°C. Beyond these times and conditions, in-use storage is the responsibility of the user.
After initial puncture: the medicinal product should be used immediately, any remaining product should be discarded.
Solution in vial requires dilution prior to administration. The prepared infusion solution is intended to be used immediately. If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution at 2ºC to 8ºC for no more than 24 hours and at room temperature up to 25°C for no more than 6 hours. Beyond these times and conditions, in-use storage is the responsibility of the user. If refrigerated, allow the IV infusion bag to equilibrate to room temperature for approximately 30 minutes prior to administration.
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 24 hours and at room temperature up to 25ºC for no more than 4 hours. Beyond these times and conditions, in-use storage is the responsibility of the user. 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 clear Type 1 glass vials in 20 mL or 6 mL vials.
Each carton contains 2 vials per package:
Ronapreve 120 mg/mL solution for infusion or injection, multidose vials:
Pack of two 20 mL clear Type I glass vials with butyl rubber stopper containing one vial of 11.1 mL solution of 1 332 mg of casirivimab and one vial of 11.1 mL solution of 1 332 mg of imdevimab.
Ronapreve 120 mg/ml solution for infusion or injection, single-use vial:
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.
Casirivimab and imdevimab vials should be inspected visually to ensure there is no particulate matter or discolouration prior to the administration. If particulate matter or discolouration is observed the vial should be discarded per local disposal guidelines.
Do not shake or freeze the vials.
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 discoloration prior to administration. Should either be observed, the vial must be discarded and replaced with a new vial.
3. Obtain a prefilled IV 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. 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
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 discoloration 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, colorless to pale yellow.
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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