RONAPREVE 120 MG/ML + 120 MG/ML INJECTABLE SOLUTION AND PERFUSION SOLUTION

2. What you need to know before you use Ronapreve

Do not use Ronapreve

• if you are allergic to casirivimab, imdevimab, or any of the other ingredients of this medicine (listed in section 6).

If you meet any of the above conditions, consult your doctor or nurse as soon as possible.

Warnings and precautions

• This medicine may cause allergic reactions or reactions after infusion or injection. The signs of these reactions are listed in Section 4. Inform your doctor immediately if you experience any of these signs or symptoms.

Children and adolescents

This medicine must not be given to children under 12 years of age or adolescents who weigh less than 40 kg.

Other medicines and Ronapreve

Before taking Ronapreve, inform your doctor or nurse if you are taking or have recently taken any other medicines.

After having taken Ronapreve:

• tell your doctor, nurse, or pharmacist that you have received this medicine to treat or prevent COVID-19
• tell your doctor, nurse, or pharmacist that you have received this medicine if you are receiving the COVID-19 vaccine.

Pregnancy and breastfeeding

Consult your doctor or nurse if you are pregnant or think you may be pregnant.

• This is because there is not enough information to ensure that this medicine is safe during pregnancy.
• This medicine will only be given if the potential benefits of treatment outweigh the potential risks to the mother and fetus.

Consult your doctor or nurse if you are breastfeeding.

• This is because it is not known if this medicine passes into breast milk or what effects it may have on the baby or milk production.
• Your doctor will help you decide whether to continue breastfeeding or start treatment with this medicine.

Driving and using machines

Ronapreve is unlikely to affect your ability to drive.

3. How to use Ronapreve

How much Ronapreve is given?

The recommended dose for the treatment and prevention of COVID-19 in adults and adolescents from 12 years of age and older who weigh more than 40 kg is 600 mg of casirivimab and 600 mg of imdevimab.

The recommended dose for the continued prevention of COVID-19 in adults and adolescents from 12 years of age and older who weigh more than 40 kg is 600 mg of casirivimab and 600 mg of imdevimab as an initial dose and subsequent doses of 300 mg of casirivimab and 300 mg of imdevimab once every four weeks.

How is this medicine given?

Casirivimab and imdevimab can be given together as a single infusion (drip) into a vein over 20 to 30 minutes or as subcutaneous injections given immediately one after the other, under the skin in different parts of the body, provided that the infusion does not delay treatment. Your doctor or nurse will decide how long you will be monitored after you are given the medicine. This is in case you have any side effects.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been reported with Ronapreve.

Infusion-related reactions

Tell your doctor immediately if you experience any of the signs of an allergic reaction or reaction listed below during or after the infusion. It may be necessary to slow down, interrupt, or stop the infusion and you may need other medicines to treat the symptoms. The signs or symptoms of an allergic reaction or infusion-related reactions may include:

Uncommon:may affect up to 1 in 100 people.

• feeling unwell (nausea)
• chills
• dizziness
• skin rash

Very rare:may affect up to 1 in 10,000 people.

• severe allergic reaction (anaphylaxis)

• itchy rash
• flushing

Subcutaneous injection-related reactions (under the skin)

Tell your doctor immediately if you experience any of the signs of a reaction related to the injection.

Common:may affect up to 1 in 10 people.

• redness, itching, bruising, swelling, pain, or itchy rash at the injection site

Uncommon:may affect up to 1 in 100 people.

• dizziness
• swelling of lymph nodes near the injection site

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ronapreve

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and label after EXP. The expiry date refers to the last day of the month stated.

Ronapreve will be stored by healthcare professionals in the hospital or clinic under the following conditions:

• Before use, store the concentrated solution of Ronapreve in the refrigerator at 2°C to 8°C. Before dilution, allow the concentrated solution to reach room temperature.
• Once diluted, Ronapreve must be used immediately. If necessary, the diluted solution bags can be stored between 2°C and 8°C for no more than 72 hours and at room temperature up to 25°C for no more than 20 hours. If refrigerated, allow the infusion solution to reach room temperature for about 30 minutes before administration.
• Prepared syringes must be administered immediately. If necessary, store the prepared syringes between 2°C and 8°C for no more than 72 hours and at room temperature up to 25°C for no more than 24 hours. If refrigerated, allow the syringes to reach room temperature for about 10 to 15 minutes before administration.

Do not administer this medicine if you notice that it contains visible particles or has changed color.

6. Container Content and Additional Information Composition of Ronapreve

• The active ingredients are casirivimab and imdevimab. Each single-use vial of 6 ml contains 300 mg of casirivimab or imdevimab.
• The other components are L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80, sucrose, and water for injectable preparations.

Appearance of the Product and Container Content

Ronapreve is a solution for injection/infusion. It is a transparent to slightly opalescent solution and colorless to pale yellow and is available in boxes containing 2 vials per pack, one vial for each active ingredient.

Marketing Authorization Holder and Manufacturer

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen Germany

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen Germany

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

This leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

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The following information is intended for healthcare professionals only.Refer to the product's summary of product characteristics for more information.

Instructions for Healthcare Professionals

Ronapreve 120 mg / ml + 120 mg/ml Solution for Injection and Infusion

Casirivimab and imdevimab should be administered together by intravenous infusion (after dilution) or consecutively by subcutaneous injection.

Casirivimab:

Each multidose vial contains 1.332 mg of casirivimab per 11.1 ml (120 mg/ml) as a transparent to slightly opalescent and colorless to pale yellow solution

Imdevimab:

Each multidose vial contains 1.332 mg of imdevimab per 11.1 ml (120 mg/ml) as a transparent to slightly opalescent and colorless to pale yellow solution

Summary of Treatment and Prevention

Ronapreve is indicated for:

• treatment of COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and do not require supplemental oxygen and who are at higher risk of progressing to severe COVID-19.
• prevention of COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg.

The recommended dose is:

• 600 mg of casirivimab and 600 mg of imdevimab, or
• 300 mg of casirivimab and 300 mg of imdevimab

Preparation for Intravenous Infusion Administration

The concentrated solution of Ronapreve should be diluted with a sodium chloride injection solution of 9 mg / ml (0.9%) or dextrose injection 5% for infusion in aseptic conditions. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

1 Remove the casirivimab and imdevimab vials from refrigerated storage and let them reach room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake the vials.

2 Visually inspect the casirivimab and imdevimab vials for particles and discoloration before administration. If either is observed, the vial should be discarded and replaced with a new one.

• The solution for each vial should be transparent to slightly opalescent, colorless to pale yellow.

3 Use an intravenous infusion bag preloaded with polyvinyl chloride (PVC) or polyolefin (PO) containing 50 ml, 100 ml, 150 ml, or 250 ml of sodium chloride injection solution 0.9% or dextrose injection 5%.

4 With a syringe and a sterile needle, withdraw the required volume of casirivimab and imdevimab from each vial and inject it into a preloaded infusion bag containing sodium chloride injection solution 0.9% or dextrose injection 5% (see Table 1).

5 Gently mix the infusion bag by inverting it. Do not shake.

6 This product does not contain preservatives, and therefore, the diluted infusion solution should be administered immediately.

• If immediate administration is not possible, store the infusion solution of casirivimab and imdevimab between 2 °C and 8 °C for no more than 72 hours and at room temperature up to 25 °C for no more than 20 hours. If refrigerated, let the infusion solution equilibrate to room temperature for approximately 30 minutes before administration.

Table 1: Recommended Dilution Instructions for Ronapreve (casirivimab and imdevimab) for Intravenous Infusion

Intravenous Infusion Administration

• Ronapreve should be administered by a healthcare professional using aseptic technique:
• Gather the recommended materials for infusion:
• • Polyvinyl chloride (PVC), PVC-coated polyethylene (PE), or polyurethane (PU) infusion equipment
  • Final filter of polyethersulfone, polysulfone, or polyamide in-line or additional 0.2 μm to 5 μm for intravenous administration.
• Connect the infusion equipment to the intravenous bag.
• Prime the infusion equipment.
• Administer the complete infusion solution in the bag via a pump or gravity through an intravenous line containing a sterile polyethersulfone, polysulfone, or polyamide filter, in-line or additional 0.2 μm to 5 μm for intravenous administration.
• The infusion should be administered over 20 to 30 minutes. The infusion rate can be slowed, interrupted, or stopped if the patient exhibits any signs of infusion-related events or other adverse reactions.
• 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 sodium chloride injection solution 0.9% or dextrose injection 5% is unknown.
• Once the infusion is complete, flush the tubing with sodium chloride injection solution 0.9% or dextrose injection 5% to ensure administration of the required dose.

Preparation of Ronapreve for Subcutaneous Injection

Remove the casirivimab and imdevimab vials from refrigerated storage and let them reach room temperature for approximately 20 minutes before preparation.

Do not expose to direct heat.

Do not shake the vials.

Visually inspect the casirivimab and imdevimab vials for particles and discoloration before administration. If either is observed, the vial should be discarded and replaced with a new one. The solution for each vial should be transparent to slightly opalescent, colorless to pale yellow.

1. Ronapreve should be prepared using the appropriate number of syringes (see Table 2). Use 3 ml or 5 ml polypropylene syringes with luer connection and 21-gauge transfer needles.
2. Using a syringe and a sterile needle, withdraw the required volume of casirivimab and imdevimab from each vial, respectively, into each syringe (see Table 2) for a total of 4 syringes for the combined dose of 1,200 mg and a total of 2 syringes for the combined dose of 600 mg. Store any remaining product according to the instructions.
3. Replace the 21-gauge transfer needle with a 25-gauge or 27-gauge needle for subcutaneous injection.
4. This product does not contain preservatives, and therefore, the prepared syringes should be administered immediately. If immediate administration is not possible, store the prepared syringes of casirivimab and imdevimab between 2 °C and 8 °C for no more than 72 hours and at room temperature up to 25 °C for no more than 24 hours. If refrigerated, let the syringes equilibrate to room temperature for approximately 10 to 15 minutes before administration.

Table 2: Preparation of Ronapreve (casirivimab and imdevimab) for Subcutaneous Injection

Administration of Ronapreve by Subcutaneous Injection

For administration of Ronapreve at a dose of 1,200 mg (600 mg of casirivimab and 600 mg of imdevimab), gather 4 syringes (Table 2) and prepare for subcutaneous injections.

• For administration of Ronapreve at a dose of 600 mg (300 mg of casirivimab and 300 mg of imdevimab), gather 2 syringes (Table 2) and prepare for subcutaneous injections.
• Due to the volume, administration of subcutaneous injections of casirivimab and imdevimab should be performed consecutively at different body sites (in the upper thigh, upper outer arm, or abdomen, avoiding 5 cm around the navel and waist.

Monitoring and Reporting of Adverse Reactions

• Monitor the patient for adverse reactions during and after infusion or injection according to current medical practice. The infusion rate can be reduced or interrupted if the patient exhibits any signs of infusion-related events or other adverse reactions. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately stop administration and initiate appropriate medications and/or supportive care.

• Report adverse reactions through the national reporting system included in Appendix V.

Storage

• Before use,store the casirivimab and imdevimab vials in a refrigerator between 2 °C and 8 °C until needed. Do not administer after the expiration date marked on the vials/boxes after the letters EXP.
• The casirivimab and imdevimab concentrates are transparent to slightly opalescent and colorless to pale yellow solutions.
• Before dilution,let the casirivimab and imdevimab vials reach room temperature (up to 25 °C).
• After initial puncture of the 6 ml vial, the medicinal product should be used immediately and any remaining product should be discarded.
• Once diluted,Ronapreve should be administered immediately. If necessary, the diluted solution can be stored for up to 20 hours at room temperature (up to 25 °C) and between 2 °C and 8 °C for no more than 72 hours. From a microbiological point of view, the prepared infusion solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and would normally not exceed 24 hours between 2 °C and 8 °C, unless the dilution has been performed in controlled and validated aseptic conditions.