B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Ronapreve 300 mg + 300 mg solution for injection/infusion

casirivimab and imdevimab

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You canhelp by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Ronapreve is and what it is used for

• 2. What you need to know before you are given Ronapreve

• 3. How Ronapreve is given to you

• 4. Possible side effects

• 5. How to store Ronapreve

• 6. Contents of the pack and other information

1. What Ronapreve is and what it is used for

What Ronapreve is

Ronapreve is made up of the active substances ‘casirivimab’ and ‘imdevimab’. Casirivimab and imdevimab are a type of protein called ‘monoclonal antibodies’.

What Ronapreve is used for

Ronapreve is used to treat adults and adolescents aged from 12 years weighing at least 40 kg with COVID-19 who:

• do not require oxygen to treat COVID-19, and
• are at increased risk for the illness becoming severe based on the evaluation of your doctor.

Ronapreve is used to prevent COVID-19 in adults and adolescents aged from 12 years weighing at least 40 kg.

How Ronapreve works

Ronapreve attaches to a protein on the surface of the coronavirus called the ‘spike protein’.This stops the virus from getting into your cells and from spreading between cells.

2. What you need to know before you are given Ronapreve

You must not be given Ronapreve

• if you are allergic to casirivimab, imdevimab, or any of the other ingredients of this medicine

(listed in section 6).

alk to your doctor or nurse as soon as possible, if this applies to you.

Warnings and precautions

• This medicine can cause allergic reactions or reactions following the infusion or injection. The signs of these reactions are listed in Section 4. Tell your doctor straight away if you get any of these signs or symptoms.

Children and adolescents

Do not give this medicine to children under 12 years of age or adolescents that weigh less than 40 kg.

Other medicines and Ronapreve

Before you have Ronapreve, tell the doctor or nurse who is giving it to you about any other medicines you are taking, or have recently taken.

After you have had Ronapreve:

• tell the doctor, nurse or pharmacist that you have had this medicine to treat or prevent COVID-19
• tell the doctor, nurse or pharmacist you have had this medicine, if you are getting a COVID-19 vaccine.

Pregnancy and breast-feeding

Tell your doctor or nurse if you are pregnant, or if you might be pregnant.

• This is because there is not enough information to be sure that this medicine is safe for use in pregnancy.
• This medicine will only be given if the potential benefits of treatment outweigh the potential risks to the mother and the unborn child.

Tell your doctor or nurse if you are breast-feeding.

• This is because it is not yet known whether this medicine passes into human breast milk – or what the effects might be on the baby or milk production.
• Your doctor will help you decide whether to keep breast-feeding or to start treatment with this medicine.

Driving and using machines

This medicine is not expected to have any effect on your ability to drive.

• 3. How Ronapreve is given to you

How much is given?

The recommended dose for treatment and prevention of COVID-19 in adults and in adolescents 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab.

The recommended dose for continuous prevention of COVID-19 in adults and in adolescents 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab as the initial dose, and the subsequent doses are 300 mg of casirivimab and 300 mg of imdevimab once every four weeks.

How is this medicine given?

Casirivimab and imdevimab may be given together as a single infusion (drip) into a vein over 20 to 30 minutes or as injections, given immediately one after the other, under the skin made at separate body sites if an infusion would 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.

Reactions following the infusion

Tell your doctor straight away if you get any of these signs of an allergic reaction or reaction listed below during or following the infusion. The infusion may need to be slowed down, interrupted or stopped and you may need others medicines to treat the symptoms. The signs or symptoms of allergic reaction or infusion-related reactions may include:

Uncommon: may affect up to 1 in 100 people

• Feeling sick (nausea)
• chills
• dizziness
• rash

Rare: may affect up to 1 in 1 000 people

• severe allergic reaction (anaphylaxis)
• itchy rash
• flushing

Reactions following the subcutaneous (under the skin) injection

Tell your doctor straight away if you get any of these signs of a reaction following the injections.

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
• swollen lymph nodes close to injection site

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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. How to store 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 vial label after EXP. The expiry date refers to the last day of that month.

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

• Before use, store unopened Ronapreve concentrated solution in a refrigerator until the day it is needed. Before diluting it, allow the concentrated solution to come up to room temperature.
• Once diluted, Ronapreve should be used immediately. If necessary, bags of diluted solution can be stored at 2 °C to 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 equilibrate to room temperature for approximately 30 minutes prior to administration.
• Prepared syringes should be used immediately. If necessary, store the prepared syringes at 2 °C to 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 equilibrate to room temperature for approximately 10–15 minutes prior to administration.

Do not use this medicine if you notice particulate matter or discolouration.

6. Contents of the pack and other information

What Ronapreve contains

• The active substances are casirivimab and imdevimab. Each 6 mL single-use vial contains 300 mg of casirivimab or 300 mg of imdevimab.
• The other ingredients are L-histidine, L-histidine monohydrochloride monohydrate,

polysorbate 80, sucrose, and water for injections.

What Ronapreve looks like and contents of the pack

Ronapreve is a solution for injection/infusion. It is a clear to slightly opalescent and colourless to pale yellow solution and is available in cartons that contain 2 vials per package, one vial for each active substance.

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien N.V. Roche S.A. Tél/Tel: +32 (0) 2 525 82 11	Lietuva UAB “Roche Lietuva” Tel: +370 5 2546799
Efc^rapufl	Luxembourg/Lu­xemburg
Pom Etnrapua EOOfl	(Voir/siehe Belgique/Belgien)
Tea: +359 2 818 44 44
Česká republika	Magyarorszag
Roche s. r. o.	Roche (Magyarorszag) Kft.
Tel: +420 – 2 20382111	Tel: +36 1 279 4500
Danmark	Malta
Roche a/s	(See Ireland)
Tlf: +45 – 36 39 99 99
Deutschland	Nederland
Roche Pharma AG	Roche Nederland B.V.
Tel: +49 (0) 7624 140	Tel: +31 (0) 348 438050

Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380	Norge Roche Norge AS Tlf: +47 – 22 78 90 00
EXXáSa Roche (Hellas) A.E. Tql: +30 210 61 66 100	Österreich Roche Austria GmbH Tel: +43 (0) 1 27739
España Roche Farma S.A. Tel: +34 – 91 324 81 00	Polska Roche Polska Sp.z o.o. Tel: +48 – 22 345 18 88.
France Roche Tél: +33 (0)1 47 61 40 00	Portugal Roche Farmacéutica Química, Lda Tel: +351 – 21 425 70 00
Hrvatska Roche d.o.o. Tel: + 385 1 47 22 333	Romania Roche Romania S.R.L. Tel: +40 21 206 47 01
Ireland Roche Products (Ireland) Ltd. Tel: +353 (0) 1 469 0700	Slovenija Roche farmacevtska družba d.o.o. Tel: +386 – 1 360 26 00
Ísland Roche a/s c/o Icepharma hf Sími: +354 540 8000	Slovenská republika Roche Slovensko, s.r.o. Tel: +421 – 2 52638201
Italia Roche S.p.A. Tel: +39 – 039 2471	Suomi/Finland Roche Oy Puh/Tel: +358 (0) 10 554 500
Kúnpog r.A.ETapArqg & Sia At5. Tql: +357 – 22 76 62 76	Sverige Roche AB Tel: +46 (0) 8 726 1200
Latvija Roche Latvija SIA Tel: +371 – 6 7039831	United Kingdom (Northern Ireland) Roche Products (Ireland) Ltd. Tel: +44 (0) 1707 366000

This leaflet was last revised in.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only. Please refer to the Summary of Product Characteristics for further information.

Instructions for healthcare professionals

Ronapreve 300 mg + 300 mg solution for injection/infusion

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

Casirivimab:

Each single-use vial contains 300 mg of casirivimab per 2.5 mL (120 mg/mL) as a clear to slightly opalescent and colourless to pale yellow solution.

Imdevimab:

Each single-use vial contains 300 mg of imdevimab per 2.5 mL (120 mg/mL) as a clear to slightly opalescent and colourless 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 weighing at least 40 kg who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.
• Prevention of COVID-19 in adults and adolescents aged 12 years and older weighing 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

Ronapreve concentrated solution must be diluted with sodium chloride 9 mg/mL (0.9%) solution or 5% dextrose injection for infusion under 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 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 Table 1).

• 5. Gently mix infusion bag by inversion. Do not shake.

• 6. This product is preservative-free and therefore, the diluted infusion solution should be administered immediately.

• If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution at 2 °C to 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 equilibrate to room temperature for approximately 30 minutes prior to administration.

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

Indication	Ronapreve Dose	Total Volume for 1 Dose	Volume to be withdrawn from each respective vial and injected into a single prefilled 0.9% sodium chloride or 5% dextrose infusion bag of 50–250 mL for coadministration
Treatment, 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
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

Administration by Intravenous Infusion

Ronapreve infusion solution should be administered by a qualified healthcare professional using aseptic technique.

• Gather the recommended materials for infusion:

o Polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set

o In-line or add-on 0.2 gm to 5 gm 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 gm to 5 gm polyethersulfone, polysulfone, or polyamide filter for intravenous administration.
• The infusion should be administered over 20–30 minutes. The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse 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 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.

Preparation 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 Table 2). Obtain 3 mL or 5 mL polypropylene syringes with luer connection and 21-gauge transfer needles.

• 2. Using a sterile syringe and needle, withdraw the appropriate volume of casirivimab and imdevimab from each respective vial into each syringe (see 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.

• 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°C to 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 equilibrate to room temperature for approximately 10–15 minutes prior to administration.

Table 2 Preparation of Ronapreve (casirivimab and 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, 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

Administration for Subcutaneous Injection

• For the administration of Ronapreve 1 200 mg dose (600 mg of casirivimab and 600 mg of imdevimab), gather 4 syringes (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 (Table 2) and prepare for subcutaneous injections.
• Due to the volume, 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).

Monitor and report side effects

• Monitor the patient for side effects during and after the infusion or injection according to current medical practice. The rate of infusion may be slowed or interrupted if the patient develops any signs of infusion-associated events or other adverse events. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.
• Report side effects via the national reporting system listed in Appendix V.

Storage

• Before use, store casirivimab and imdevimab vials in a fridge between 2 °C to 8 °C until they are required. Do not use after expiry date, marked on the vials/cartons after the letters EXP.
• Casirivimab and imdevimab concentrates are clear to slightly opalescent and colourless to pale yellow solutions.
• Before dilution, allow casirivimab and imdevimab vials to warm up to 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, bags of diluted solution can be stored for up to 20 hours at room temperature (up to 25 °C) and 2 °C to 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, 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.

Package leaflet: Information for the patient

Ronapreve 120 mg/mL + 120 mg/mL solution for injection/infusion

casirivimab and imdevimab

This medicine is subject to additional monitoring. This will allow quick identification of new safetyinformation. You canhelp by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Ronapreve is and what it is used for

• 2. What you need to know before you are given Ronapreve

• 3. How Ronapreve is given to you

• 4. Possible side effects

• 5. How to store Ronapreve

• 6. Contents of the pack and other information

1. What Ronapreve is and what it is used for

What Ronapreve is

Ronapreve is made up of the active substances ‘casirivimab’ and ‘imdevimab’. Casirivimab and imdevimab are a type of protein called ‘monoclonal antibodies’.

What Ronapreve is used for

Ronapreve is used to treat adults and adolescents aged from 12 years weighing at least 40 kg with

COVID-19 who:

• do not require oxygen to treat COVID-19, and
• are at increased risk for the illness becoming severe based on the evaluation of your doctor.

Ronapreve is used to prevent COVID-19 in adults and adolescents aged from 12 years weighing at least 40 kg.

How Ronapreve works

Ronapreve attaches to a protein on the surface of the coronavirus called the ‘spike protein’.This stops the virus from getting into your cells and from spreading between cells.

2. What you need to know before you are given Ronapreve

You must not be given Ronapreve

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

Talk to your doctor or nurse as soon as possible, if this applies to you.

Warnings and precautions

• This medicine can cause allergic reactions or reactions following the infusion or injection. The signs of these reactions are listed in Section 4. Tell your doctor straight away if you get any of these signs or symptoms.

Children and adolescents

Do not give this medicine to children under 12 years of age or adolescents that weigh less than 40 kg.

Other medicines and Ronapreve

Before you have Ronapreve, tell the doctor or nurse who is giving it to you about any other medicines you are taking, or have recently taken.

After you have had Ronapreve:

• tell the doctor, nurse or pharmacist that you have had this medicine to treat or prevent COVID-19
• tell the doctor, nurse or pharmacist you have had this medicine, if you are getting a COVID-19 vaccine.

Pregnancy and breast-feeding

Tell your doctor or nurse if you are pregnant, or if you might be pregnant.

• This is because there is not enough information to be sure that this medicine is safe for use in pregnancy.
• This medicine will only be given if the potential benefits of treatment outweigh the potential risks to the mother and the unborn child.

Tell your doctor or nurse if you are breast-feeding.

• This is because it is not yet known whether this medicine passes into human breast milk – or what the effects might be on the baby or milk production.
• Your doctor will help you decide whether to keep breast-feeding or to start treatment with this medicine.

Driving and using machines

This medicine is not expected to have any effect on your ability to drive.

• 3. How Ronapreve is given to you

How much is given?

The recommended dose for treatment and prevention of COVID-19 in adults and in adolescents 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab.

The recommended dose for continuous prevention of COVID-19 in adults and in adolescents 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab as the initial dose, and the subsequent doses are 300 mg of casirivimab and 300 mg of imdevimab once every four weeks.

How is this medicine given?

Casirivimab and imdevimab may be given together as a single infusion (drip) into a vein over 20 to 30 minutes or as injections, given immediately one after the other, under the skin made at separate body sites if an infusion would 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.

Reactions following the infusion

Tell your doctor straight away if you get any of these signs of an allergic reaction or reaction listed below during or following the infusion. The infusion may need to be slowed down, interrupted or stopped and you may need others medicines to treat the symptoms. The signs or symptoms of allergic reaction or infusion-related reactions may include:

Uncommon: may affect up to 1 in 100 people

• Feeling sick (nausea)
• chills
• dizziness
• rash

Rare: may affect up to 1 in 1 000 people

• severe allergic reaction (anaphylaxis)
• itchy rash
• flushing

Reactions following the subcutaneous (under the skin) injection

Tell your doctor straight away if you get any of these signs of a reaction following the injections.

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
• swollen lymph nodes close to injection site

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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. How to store 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 vial label after EXP. The expiry date refers to the last day of that month.

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

• Before use, store unopened Ronapreve concentrated solution in a refrigerator until the day it is needed. Before diluting it, allow the concentrated solution to come up to room temperature.
• Once diluted, Ronapreve should be used immediately. If necessary, bags of diluted solution can be stored at 2 °C to 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 equilibrate to room temperature for approximately 30 minutes prior to administration.
• Prepared syringes should be used immediately. If necessary, store the prepared syringes at 2 °C to 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 equilibrate to room temperature for approximately 10–15 minutes prior to administration.

Do not use this medicine if you notice particulate matter or discolouration.

6. Contents of the pack and other information

What Ronapreve contains

• The active substances are casirivimab and imdevimab. Each 20 mL multidose vial contains

• 1 332 mg of casirivimab or 1 332 mg of imdevimab.

• The other ingredients are L-histidine, L-histidine monohydrochloride monohydrate,

polysorbate 80, sucrose, and water for injections.

What Ronapreve looks like and contents of the pack

Ronapreve is a solution for injection/infusion. It is a clear to slightly opalescent and colourless to pale yellow solution and is available in cartons that contain 2 vials per package, one vial for each active substance.

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien N.V. Roche S.A. Tél/Tel: +32 (0) 2 525 82 11	Lietuva UAB “Roche Lietuva” Tel: +370 5 2546799
Efc^rapufl	Luxembourg/Lu­xemburg
Pom Etnrapua EOOfl	(Voir/siehe Belgique/Belgien)
Tea: +359 2 818 44 44
Česká republika	Magyarorszag
Roche s. r. o.	Roche (Magyarorszag) Kft.
Tel: +420 – 2 20382111	Tel: +36 1 279 4500
Danmark	Malta
Roche a/s	(See Ireland)
Tlf: +45 – 36 39 99 99
Deutschland	Nederland
Roche Pharma AG	Roche Nederland B.V.
Tel: +49 (0) 7624 140	Tel: +31 (0) 348 438050

Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380	Norge Roche Norge AS Tlf: +47 – 22 78 90 00
EXXáSa Roche (Hellas) A.E. Tql: +30 210 61 66 100	Österreich Roche Austria GmbH Tel: +43 (0) 1 27739
España Roche Farma S.A. Tel: +34 – 91 324 81 00	Polska Roche Polska Sp.z o.o. Tel: +48 – 22 345 18 88.
France Roche Tél: +33 (0)1 47 61 40 00	Portugal Roche Farmacéutica Química, Lda Tel: +351 – 21 425 70 00
Hrvatska Roche d.o.o. Tel: + 385 1 47 22 333	Romania Roche Romania S.R.L. Tel: +40 21 206 47 01
Ireland Roche Products (Ireland) Ltd. Tel: +353 (0) 1 469 0700	Slovenija Roche farmacevtska družba d.o.o. Tel: +386 – 1 360 26 00
Ísland Roche a/s c/o Icepharma hf Sími: +354 540 8000	Slovenská republika Roche Slovensko, s.r.o. Tel: +421 – 2 52638201
Italia Roche S.p.A. Tel: +39 – 039 2471	Suomi/Finland Roche Oy Puh/Tel: +358 (0) 10 554 500
Kúnpog r.A.ETapArqg & Sia At5. Tql: +357 – 22 76 62 76	Sverige Roche AB Tel: +46 (0) 8 726 1200
Latvija Roche Latvija SIA Tel: +371 – 6 7039831	United Kingdom (Northern Ireland) Roche Products (Ireland) Ltd. Tel: +44 (0) 1707 366000

This leaflet was last revised in.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only. Please refer to the Summary of Product Characteristics for further information.

Instructions for healthcare professionals

Ronapreve 300 mg + 300 mg solution for injection/infusion

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

Casirivimab:

Each single-use vial contains 300 mg of casirivimab per 2.5 mL (120 mg/mL) as a clear to slightly opalescent and colourless to pale yellow solution.

Imdevimab:

Each single-use vial contains 300 mg of imdevimab per 2.5 mL (120 mg/mL) as a clear to slightly opalescent and colourless 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 weighing at least 40 kg who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.
• Prevention of COVID-19 in adults and adolescents aged 12 years and older weighing 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

Ronapreve concentrated solution must be diluted with sodium chloride 9 mg/mL (0.9%) solution or 5% dextrose injection for infusion under 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 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 Table 1).

• 5. Gently mix infusion bag by inversion. Do not shake.

• 6. This product is preservative-free and therefore, the diluted infusion solution should be administered immediately.

• If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution at 2 °C to 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 equilibrate to room temperature for approximately 30 minutes prior to administration.

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

Indication	Ronapreve Dose	Total Volume for 1 Dose	Volume to be withdrawn from each respective vial and injected into a single prefilled 0.9% sodium chloride or 5% dextrose infusion bag of 50–250 mL for coadministration
Treatment, 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
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

Administration by Intravenous Infusion

Ronapreve infusion solution should be administered by a qualified healthcare professional using aseptic technique.

• Gather the recommended materials for infusion:

o Polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set

o In-line or add-on 0.2 gm to 5 gm 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 gm to 5 gm polyethersulfone, polysulfone, or polyamide filter for intravenous administration.
• The infusion should be administered over 20–30 minutes. The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse 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 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.

Preparation 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 Table 2). Obtain 3 mL or 5 mL polypropylene syringes with luer connection and 21-gauge transfer needles.

• 2. Using a sterile syringe and needle, withdraw the appropriate volume of casirivimab and imdevimab from each respective vial into each syringe (see 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.

• 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°C to 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 equilibrate to room temperature for approximately 10–15 minutes prior to administration.

Table 2 Preparation of Ronapreve (casirivimab and 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, 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

Administration for Subcutaneous Injection

• For the administration of Ronapreve 1 200 mg dose (600 mg of casirivimab and 600 mg of imdevimab), gather 4 syringes (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 (Table 2) and prepare for subcutaneous injections.
• Due to the volume, 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).

Monitor and report side effects

• Monitor the patient for side effects during and after the infusion or injection according to current medical practice. The rate of infusion may be slowed or interrupted if the patient develops any signs of infusion-associated events or other adverse events. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.
• Report side effects via the national reporting system listed in Appendix V.

Storage

• Before use, store casirivimab and imdevimab vials in a fridge between 2 °C to 8 °C until they are required. Do not use after expiry date, marked on the vials/cartons after the letters EXP.
• Casirivimab and imdevimab concentrates are clear to slightly opalescent and colourless to pale yellow solutions.
• Before dilution, allow casirivimab and imdevimab vials to warm up to 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, bags of diluted solution can be stored for up to 20 hours at room temperature (up to 25 °C) and 2 °C to 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, 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.

Package leaflet: Information for the patient

Ronapreve 120 mg/mL + 120 mg/mL solution for injection/infusion

casirivimab and imdevimab

This medicine is subject to additional monitoring. This will allow quick identification of new safetyinformation. You canhelp by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Ronapreve is and what it is used for

• 2. What you need to know before you are given Ronapreve

• 3. How Ronapreve is given to you

• 4. Possible side effects

• 5. How to store Ronapreve

• 6. Contents of the pack and other information

1. What Ronapreve is and what it is used for

What Ronapreve is

Ronapreve is made up of the active substances ‘casirivimab’ and ‘imdevimab’. Casirivimab and imdevimab are a type of protein called ‘monoclonal antibodies’.

What Ronapreve is used for

Ronapreve is used to treat adults and adolescents aged from 12 years weighing at least 40 kg with

COVID-19 who:

• do not require oxygen to treat COVID-19, and
• are at increased risk for the illness becoming severe based on the evaluation of your doctor.

Ronapreve is used to prevent COVID-19 in adults and adolescents aged from 12 years weighing at least 40 kg.

How Ronapreve works

Ronapreve attaches to a protein on the surface of the coronavirus called the ‘spike protein’.This stops the virus from getting into your cells and from spreading between cells.

2. What you need to know before you are given Ronapreve

You must not be given Ronapreve

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

Talk to your doctor or nurse as soon as possible, if this applies to you.

Warnings and precautions

• This medicine can cause allergic reactions or reactions following the infusion or injection. The signs of these reactions are listed in Section 4. Tell your doctor straight away if you get any of these signs or symptoms.

Children and adolescents

Do not give this medicine to children under 12 years of age or adolescents that weigh less than 40 kg.

Other medicines and Ronapreve

Before you have Ronapreve, tell the doctor or nurse who is giving it to you about any other medicines you are taking, or have recently taken.

After you have had Ronapreve:

• tell the doctor, nurse or pharmacist that you have had this medicine to treat or prevent COVID-19
• tell the doctor, nurse or pharmacist you have had this medicine, if you are getting a COVID-19 vaccine.

Pregnancy and breast-feeding

Tell your doctor or nurse if you are pregnant, or if you might be pregnant.

• This is because there is not enough information to be sure that this medicine is safe for use in pregnancy.
• This medicine will only be given if the potential benefits of treatment outweigh the potential risks to the mother and the unborn child.

Tell your doctor or nurse if you are breast-feeding.

• This is because it is not yet known whether this medicine passes into human breast milk – or what the effects might be on the baby or milk production.
• Your doctor will help you decide whether to keep breast-feeding or to start treatment with this medicine.

Driving and using machines

This medicine is not expected to have any effect on your ability to drive.

• 3. How Ronapreve is given to you

How much is given?

The recommended dose for treatment and prevention of COVID-19 in adults and in adolescents 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab.

The recommended dose for continuous prevention of COVID-19 in adults and in adolescents 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab as the initial dose, and the subsequent doses are 300 mg of casirivimab and 300 mg of imdevimab once every four weeks.

How is this medicine given?

Casirivimab and imdevimab may be given together as a single infusion (drip) into a vein over 20 to 30 minutes or as injections, given immediately one after the other, under the skin made at separate body sites if an infusion would 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.

Reactions following the infusion

Tell your doctor straight away if you get any of these signs of an allergic reaction or reaction listed below during or following the infusion. The infusion may need to be slowed down, interrupted or stopped and you may need others medicines to treat the symptoms. The signs or symptoms of allergic reaction or infusion-related reactions may include:

Uncommon: may affect up to 1 in 100 people

• Feeling sick (nausea)
• chills
• dizziness
• rash

Rare: may affect up to 1 in 1 000 people

• severe allergic reaction (anaphylaxis)
• itchy rash
• flushing

Reactions following the subcutaneous (under the skin) injection

Tell your doctor straight away if you get any of these signs of a reaction following the injections.

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
• swollen lymph nodes close to injection site

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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. How to store 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 vial label after EXP. The expiry date refers to the last day of that month.

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

• Before use, store unopened Ronapreve concentrated solution in a refrigerator until the day it is needed. Before diluting it, allow the concentrated solution to come up to room temperature.
• Once diluted, Ronapreve should be used immediately. If necessary, bags of diluted solution can be stored at 2 °C to 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 equilibrate to room temperature for approximately 30 minutes prior to administration.
• Prepared syringes should be used immediately. If necessary, store the prepared syringes at 2 °C to 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 equilibrate to room temperature for approximately 10–15 minutes prior to administration.

Do not use this medicine if you notice particulate matter or discolouration.

6. Contents of the pack and other information

What Ronapreve contains

• The active substances are casirivimab and imdevimab. Each 20 mL multidose vial contains

• 1 332 mg of casirivimab or 1 332 mg of imdevimab.

• The other ingredients are L-histidine, L-histidine monohydrochloride monohydrate,

polysorbate 80, sucrose, and water for injections.

What Ronapreve looks like and contents of the pack

Ronapreve is a solution for injection/infusion. It is a clear to slightly opalescent and colourless to pale yellow solution and is available in cartons that contain 2 vials per package, one vial for each active substance.

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1 79639 Grenzach-Wyhlen Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien

N.V. Roche S.A.

Tél/Tel: +32 (0) 2 525 82 11

Luxembourg/Lu­xemburg

(Voir/siehe Belgique/Belgien)

Magyarország

Roche (Magyarország) Kft.

Tel: +36 1 279 4500

Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380	Norge Roche Norge AS Tlf: +47 – 22 78 90 00
EXXáSa Roche (Hellas) A.E. Tql: +30 210 61 66 100	Österreich Roche Austria GmbH Tel: +43 (0) 1 27739
España Roche Farma S.A. Tel: +34 – 91 324 81 00	Polska Roche Polska Sp.z o.o. Tel: +48 – 22 345 18 88.
France Roche Tél: +33 (0)1 47 61 40 00	Portugal Roche Farmacéutica Química, Lda Tel: +351 – 21 425 70 00
Hrvatska Roche d.o.o. Tel: + 385 1 47 22 333	Romania Roche Romania S.R.L. Tel: +40 21 206 47 01
Ireland Roche Products (Ireland) Ltd. Tel: +353 (0) 1 469 0700	Slovenija Roche farmacevtska družba d.o.o. Tel: +386 – 1 360 26 00
Ísland Roche a/s c/o Icepharma hf Sími: +354 540 8000	Slovenská republika Roche Slovensko, s.r.o. Tel: +421 – 2 52638201
Italia Roche S.p.A. Tel: +39 – 039 2471	Suomi/Finland Roche Oy Puh/Tel: +358 (0) 10 554 500
Kúnpog r.A.ETapArqg & Sia At5. Tql: +357 – 22 76 62 76	Sverige Roche AB Tel: +46 (0) 8 726 1200
Latvija Roche Latvija SIA Tel: +371 – 6 7039831	United Kingdom (Northern Ireland) Roche Products (Ireland) Ltd. Tel: +44 (0) 1707 366000

This leaflet was last revised in.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only. Please refer to the Summary of Product Characteristics for further information.

Instructions for healthcare professionals

Ronapreve 120 mg/mL + 120 mg/mL solution for injection/infusion

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

Casirivimab:

Each multidose vial contains 1 332 mg of casirivimab per 11.1 mL (120 mg/mL) as a clear to slightly opalescent and colourless to pale yellow solution.

Imdevimab:

Each multidose vial contains 1 332 mg of imdevimab per 11.1 mL (120 mg/mL) as a clear to slightly opalescent and colourless 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 weighing at least

40 kg who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.

• Prevention of COVID-19 in adults and adolescents aged 12 years and older weighing 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

Ronapreve concentrated solution must be diluted with sodium chloride 9 mg/mL (0.9%) solution or 5% dextrose injection for infusion under 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 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 Table 1).

• 5. Gently mix infusion bag by inversion. Do not shake.

• 6. This product is preservative-free and therefore, the diluted infusion solution should be administered immediately.

• If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution at 2 °C to 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 equilibrate to room temperature for approximately 30 minutes prior to administration.

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

Indication	Ronapreve Dose	Total Volume for 1 Dose	Volume to be withdrawn from each respective vial and injected into a single prefilled 0.9% sodium chloride or 5% dextrose infusion bag of 50–250 mL for coadministration
Treatment, Post-exposure prophylaxis (single dose), Pre-exposure prophylaxis (initial dose)	600 mg casirivimab and 600 mg imdevimab	10 mL	5 mL from one 1 332 mg multidose vial of casirivimab 5 mL from one 1 332 mg multidose vial of imdevimab
Pre-exposure prophylaxis (repeat dose)	300 mg casirivimab and 300 mg imdevimab	5 mL	2.5 mL from one 1 332 mg multidose vial of casirivimab 2.5 mL from one 1 332 mg multidose vial of imdevimab

Administration by Intravenous Infusion

Ronapreve infusion solution should be administered by a qualified healthcare professional using aseptic technique.

• Gather the recommended materials for infusion:

o Polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set

o In-line or add-on 0.2 gm to 5 gm 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 gm to 5 gm polyethersulfone, polysulfone, or polyamide filter for intravenous administration.
• The infusion should be administered over 20–30 minutes. The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse 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 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.

Preparation 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 Table 2). Obtain 3 mL or 5 mL polypropylene syringes with luer connection and 21-gauge transfer needles.

• 2. Using a sterile syringe and needle, withdraw the appropriate volume of casirivimab and imdevimab from each respective vial into each syringe (see 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.

• 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°C to 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 equilibrate to room temperature for approximately 10–15 minutes prior to administration.

Table 2 Preparation of Ronapreve (casirivimab and 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, Post-exposure prophylaxis (single dose), Pre-exposure prophylaxis (initial dose)	600 mg casirivimab and 600 mg imdevimab	10 mL	2.5 mL (2x) from one 1 332 mg multidose vial of casirivimab 2.5 mL (2x) from one 1 332 mg multidose vial 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 1 332 mg multidose vial of casirivimab 2.5 mL from one 1 332 mg multidose vial of imdevimab

Administration for Subcutaneous Injection

• For the administration of Ronapreve 1 200 mg dose (600 mg of casirivimab and 600 mg of imdevimab), gather 4 syringes (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 (Table 2) and prepare for subcutaneous injections.
• Due to the volume, 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).

Monitor and report side effects

• Monitor the patient for side effects during and after the infusion or injection according to current medical practice. The rate of infusion may be slowed or interrupted if the patient develops any signs of infusion-associated events or other adverse events. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.
• Report side effects via the national reporting system listed in Appendix V.

Storage

• Before use, store casirivimab and imdevimab vials in a fridge between 2 °C to 8 °C until they are required. Do not use after expiry date, marked on the vials/cartons after the letters EXP.
• Casirivimab and imdevimab concentrates are clear to slightly opalescent and colourless to pale yellow solutions.
• Before dilution, allow casirivimab and imdevimab vials to warm up to room temperature (up to 25 °C).
• After initial puncture of the 20 mL vial, if not used immediately, the medicinal product in the vial can be stored for 16 hours at room temperature up to 25 °C or for 48 hours in a refrigerator (2 °C to 8 °C). Other in-use storage times and conditions are the responsibility of the user.
• Once diluted, Ronapreve should be administered immediately. If necessary, bags of diluted solution can be stored for up to 20 hours at room temperature (up to 25 °C) and 2 °C to 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, 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.