Kevzara - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Kevzara 150 mg solution for injection in pre-filled syringe

Kevzara 200 mg solution for injection in pre-filled syringe Sarilumab

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help 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 start using 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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

In addition to this leaflet, you will be given a patient alert card, which contains important safety information that you need before and during treatment with Kevzara.

What is in this leaflet

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

• 2. What you need to know before you use Kevzara

• 3. How to use Kevzara

• 4. Possible side effects

• 5. How to store Kevzara

• 6. Contents of the pack and other information

1. What Kevzara is and what it is used for

What Kevzara is

Kevzara contains the active substance sarilumab. It is a type of protein called a monoclonal antibody.

What Kevzara is used for

Kevzara is used to treat adults with moderately to severely active rheumatoid arthritis if previous therapy did not work well enough or was not tolerated. Kevzara can be used alone or together with a medicine called methotrexate.

It may help you by:

• slowing down damage to joints
• improving your ability to perform daily activities.

How Kevzara works

• Kevzara attaches to another protein called interleukin-6 (IL-6) receptor and blocks its action.
• IL-6 plays a major role in the symptoms of rheumatoid arthritis such as pain, swollen joints, morning stiffness, and fatigue.

2. What you need to know before you use Kevzara

Do not use Kevzara:

• if you are allergic to sarilumab or any of the other ingredients of this medicine (listed in section 6).
• if you have an active severe infection.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse if:

• you have any infection or you get a lot of infections. Kevzara can lower your body's ability to fight infection: this means it can make you more likely to get infections or make your infection worse.
• you have tuberculosis (TB), symptoms of TB (persistent cough, weight loss, listlessness, mild fever), or have been in close contact with someone with TB. Before you are given Kevzara, your doctor will check you for TB.
• you have had viral hepatitis or other liver disease. Before you use Kevzara, your doctor will do a blood test to check your liver function.
• you have had diverticulitis (a condition of the lower bowel) or ulcers in your stomach or intestines, or develop symptoms such as fever and stomach (abdominal) pain that does not go away.
• you have ever had any type of cancer.
• you have recently had any vaccination or are going to have a vaccination.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before using Kevzara.

You will have blood tests before you are given Kevzara. You will also have the tests during your treatment. This is to check for low blood cell count, liver problems, or changes in your cholesterol levels.

Children and adolescents

Kevzara is not recommended in children and adolescents under 18 years of age.

Other medicines and Kevzara

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This is because Kevzara can affect the way some other medicines work. Also some other medicines can affect the way Kevzara works.

In particular, do not use Kevzara and tell your doctor or pharmacist if you are using:

• a group of medicines called “Janus kinase (JAK) inhibitors” (used for diseases like rheumatoid arthritis and cancer)
• other biological medicines used in the treatment of rheumatoid arthritis

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist.

Kevzara can affect the way some medicines work: this means the dose of other medicines may need changing. If you are using any of the following medicines, tell your doctor or pharmacist before using Kevzara:

• statins, used to reduce cholesterol level
• oral contraceptives
• theophylline, used to treat asthma
• warfarin, used to prevent blood clots.

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist.

Pregnancy and breast-feeding

Talk to your doctor before using Kevzara if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby.

• Do not take Kevzara if you are pregnant unless your doctor specifically recommends it.
• The effects of Kevzara on an unborn baby are not known.
• You and your doctor should decide if you should use Kevzara if you are breast-feeding.

Driving and using machines

The use of Kevzara is not expected to affect your ability to drive or use machines. However, if you are feeling tired or unwell after you use Kevzara, you should not drive or use machines.

3. How to use Kevzara

Treatment should be started by a doctor experienced in the diagnosis and treatment of rheumatoid arthritis. Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Kevzara is given as an injection under the skin (called “subcutaneous” injection).

The recommended dose is one 200 mg injection every two weeks.

• Your doctor may adjust the dose of your medicine based on results of blood tests.

Learning how to use the pre-filled syringe

• Your doctor, pharmacist, or nurse will show you how to inject Kevzara. Following these instructions, Kevzara can be self-injected or administered by a care-giver.
• Carefully follow the “Instructions for Use” provided in the carton.
• Use the pre-filled syringe exactly as described in the “Instructions for Use”.

If you use more Kevzara than you should

If you have used more Kevzara than you should, talk to your doctor, pharmacist or nurse.

If you miss a dose of Kevzara

If it has been 3 days or less since the missed dose:

• inject your missed dose as soon as you can.
• then inject your next dose at your regular time.

If it has been 4 days or more, inject the next dose at your regular time. Do not inject a double dose to make up for a forgotten injection.

If you are unsure when to inject your next dose: ask your doctor, pharmacist or nurse for instructions.

If you stop using Kevzara

Do not stop using Kevzara without talking to your doctor.

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.

Serious side effect

Tell your doctor straight away if you think you have an infection (which may affect up to 1 in every 10 people). The symptoms may include fever, sweats, or chills.

Other side effects

Tell your doctor, pharmacist, or nurse if you notice any of the following side effects:

Very Common (may affect more than 1 in 10 people):

• Low white blood cell counts shown by blood tests

Common (may affect up to 1 in 10 people):

• infections in your sinuses or throat, blocked or runny nose and sore throat (upper respiratory tract infection)
• urinary tract infection
• cold sores (oral herpes)
• low platelet counts shown by blood tests
• high cholesterol, high triglycerides shown by blood tests
• abnormal liver function tests
• injection-site reactions (including redness and itching).

Uncommon (may affect up to 1 in 100 people):

• infection of the lungs
• inflammation of the deep skin tissue
• diverticulitis (a disease affecting the gut often with stomach (abdominal) pain, nausea and vomiting, fever, and constipation, or less commonly diarrhoea)

Rare (may affect up to 1 in 1000 people):

• perforation in stomach or intestines (a hole that develops in the wall of the gut)

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 Kevzara

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 label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C).

• Do not freeze or heat the syringe.
• Once taken out of the refrigerator, do not store Kevzara above 25 °C.
• Write down the date of removal from the refrigerator in the space provided on the outer carton.
• Use the syringe within 14 days after taking it out of the refrigerator or the insulated bag.
• Keep the syringe in the original carton in order to protect it from light.

Do not use this medicine if the solution in the syringe is cloudy, discoloured or contains particles, or if any part of the pre-filled syringe looks damaged.

After use, put the syringe into a puncture-resistant container. Always keep the container out of the sight and reach of children. Ask your doctor, pharmacist, or nurse how to throw away the container. Do not recycle the container.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Kevzara contains

• The active substance is sarilumab.
• The other ingredients are arginine, histidine, polysorbate 20, sucrose, and water for injections.

What Kevzara looks like and contents of the pack

Kevzara is a clear, colourless to pale yellow solution for injection that comes in a pre-filled syringe.

Each pre-filled syringe contains 1.14 ml of solution delivering one single dose. It is available in pack sizes of 1 or 2 or a multipack of 6 pre-filled syringes (3 packs of 2).

Not all pack sizes may be marketed.

Kevzara is available as 150 mg or 200 mg pre-filled syringes.

Marketing Authorisation Holder

sanofi-aventis groupe

54, rue La Boétie

F-75008 Paris

France

Manufacturer

Sanofi Winthrop Industrie

1051 Boulevard Industriel

76580 Le Trait,

France

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

España sanofi-aventis, S.A. Tel: +34 93 485 94 00	Polska sanofi-aventis Sp. z o.o. Tel.: +48 22 280 00 00
France sanofi-aventis france Tél: 0 800 222 555 Appel depuis l’étranger : +33 1 57 63 23 23	Portugal Sanofi – Produtos Farmacéuticos, Lda Tel: +351 21 35 89 400
Hrvatska Swixx Biopharma d.o.o. Tel: +385 1 2078 500	Romania Sanofi Romania SRL Tel: +40 (0) 21 317 31 36
Ireland sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +353 (0) 1 403 56 00	Slovenija Swixx Biopharma d.o.o. Tel: +386 1 235 51 00
Ísland Vistor hf. Sími: +354 535 7000	Slovenská republika Swixx Biopharma s.r.o. Tel: +421 2 208 33 600
Italia Sanofi S.r.l. Tel: 800 13 12 12 (domande di tipo tecnico) 800 536389 (altre domande)	Suomi/Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300
Kùnpoç C.A. Papaellinas Ltd. Tnk +357 22 741741	Sverige Sanofi AB Tel: +46 (0)8 634 50 00
Latvija Swixx Biopharma SIA Tel: +371 6 616 47 50	United Kingdom Sanofi Tel: +44 (0) 845 372 7101

This leaflet was last revised in.

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

Kevzara 150 mg solution for injection in a pre-filled syringe sarilumab

Instructions for use

The parts of the Kevzara pre-filled syringe are shown in this picture.

This device is a single-dose pre-filled syringe (called “syringe” in these instructions). It contains 150 mg of Kevzara for injection under the skin (subcutaneous injection) once every two weeks.

Ask your healthcare professional to show you the right way to use the syringe before your first injection.

Do

S Read all of the instructions carefully before using a syringe.

S Check that you have the correct medicine and the correct dose.

S Keep unused syringes in the original carton and store in the refrigerator between 2°C and 8°C.

S Keep the carton in an insulated bag with an ice pack when travelling.

S Let the syringe warm up to room temperature for at least 30 minutes before using.

S Use the syringe within 14 days after taking it out of the refrigerator or insulated bag.

S Keep the syringe out of the sight and reach of children.

Do not

D Do not use the syringe if it has been damaged or the needle cap is missing or not attached.

D Do not remove the needle cap until just before you are ready to inject.

D Do not touch the needle.

D Do not try to put the cap back on the syringe.

D Do not re-use the syringe.

D Do not freeze or heat the syringe.

O Once removed from the refrigerator, do not store the syringe above 25°C.

D Do not expose the syringe to direct sunlight.

D Do not inject through your clothes.

If you have any further questions, ask your doctor, pharmacist or nurse or call the sanofi number on the package leaflet.

Step A: Get ready for an injection

• 1. Prepare all the equipment you will need on a clean, flat working surface.

• You will need an alcohol wipe, a cotton ball or gauze, and a puncture-resistant container.
• Take one syringe out of the packaging by holding the middle of the syringe body. Keep the remaining syringe in the carton in the refrigerator.

• 2. Look at the label.

• Check that you have the correct medicine and the correct dose.
• Check the expiry date (EXP).

D Do not use the syringe if the date has passed.

• 3. Look at the medicine.

• Check that the liquid is clear and colourless to pale yellow.
• You may see an air bubble, this is normal.

D Do not inject if the liquid is cloudy, discoloured or contains particles.

• 4. Lay the syringe on a flat surface and allow it to warm up to room temperature (<25°C) for at least 30 minutes.

• Using the syringe at room temperature may make the injection more comfortable.

D Do not use the syringe if it has been out of the refrigerator for more than 14 days.

D Do not heat the syringe; let it warm up on its own.

D Do not expose the syringe to direct sunlight.

• 5. Select the injection site.

• You can inject into your thigh or belly (abdomen) except for the 5 cm around your belly button (navel). If somebody else gives you the injection, you can also use the outer area of the upper arm.
• Change injection site each time you inject.

D Do not inject into skin that is tender, damaged or has bruises or scars.

• 6. Prepare the injection site.

• Wash your hands.
• Clean skin with an alcohol wipe.

D Do not touch the injection site again before the injection.

Step B: Perform the injection – Perform Step B only after completing Step A “Get ready for an injection”

• 1. Pull off the needle cap.

• Hold the syringe in the middle of the syringe body with the needle pointing away from you.
• Keep your hand away from the plunger.

D Do not get rid of any air bubbles in the syringe.

• 4. Push the plunger down.

• Slowly push the plunger down as far as it will go until the syringe is empty.

• 5. Before you remove the needle, check that the syringe is empty.

• Pull the needle out at the same angle it was injected.
• If you see any blood, press a cotton ball or gauze on the site.

D Do not rub your skin after the injection.

• 6. Put your used syringe and the cap into a puncture-resistant container right away after use.

• Always keep the container out of the sight and reach of children.

D Do not put the needle cap back on.

D Do not throw the used syringe in household waste.

D Do not recycle your used puncture-resistant container.

D Do not dispose of your used puncture-resistant container in your household waste unless your local guidelines permit this. Ask your doctor, pharmacist or nurse how to throw away the container.

Kevzara 200 mg solution for injection in a pre-filled syringe sarilumab

Instructions for use

The parts of the Kevzara pre-filled syringe are shown in this picture.

Important information

This device is a single-dose pre-filled syringe (called “syringe” in these instructions). It contains 200 mg of Kevzara for injection under the skin (subcutaneous injection) once every two weeks.

Ask your healthcare professional to show you the right way to use the syringe before your first injection.

Do

S Read all of the instructions carefully before using a syringe.

S Check that you have the correct medicine and the correct dose.

S Keep unused syringes in the original carton and store in the refrigerator between 2°C and 8°C.

S Keep the carton in an insulated bag with an ice pack when travelling.

S Let the syringe warm up to room temperature for at least 30 minutes before using.

S Use the syringe within 14 days after taking it out of the refrigerator or insulated bag.

S Keep the syringe out of the sight and reach of children.

Do not

D Do not use the syringe if it has been damaged or the needle cap is missing or not attached.

D Do not remove the needle cap until just before you are ready to inject.

D Do not touch the needle.

D Do not try to put the cap back on the syringe.

D Do not re-use the syringe.

D Do not freeze or heat the syringe.

O Once removed from the refrigerator, do not store the syringe above 25°C.

D Do not expose the syringe to direct sunlight.

D Do not inject through your clothes.

If you have any further questions, ask your doctor, pharmacist or nurse or call the sanofi number on the package leaflet.

Step A: Get ready for an injection

• 1. Prepare all the equipment you will need on a clean, flat working surface.

• You will need an alcohol wipe, a cotton ball or gauze, and a puncture-resistant container.
• Take one syringe out of the packaging by holding the middle of the syringe body. Keep the remaining syringe in the carton in the refrigerator.

• 2. Look at the label.

• Check that you have the correct medicine and the correct dose.
• Check the expiry date (EXP).

D Do not use the syringe if the date has passed.

• 3. Look at the medicine.

• Check that the liquid is clear and colourless to pale yellow.
• You may see an air bubble, this is normal.

D Do not inject if the liquid is cloudy, discoloured or contains particles.

• 4. Lay the syringe on a flat surface and allow it to warm up to room temperature (<25°C) for at least 30 minutes.

• Using the syringe at room temperature may make the injection more comfortable.

D Do not use the syringe if it has been out of the refrigerator for more than 14 days.

D Do not heat the syringe; let it warm up on its own.

D Do not expose the syringe to direct sunlight.

• 5. Select the injection site.

• You can inject into your thigh or belly (abdomen) except for the 5 cm around your belly button (navel). If somebody else gives you the injection, you can also use the outer area of the upper arm.
• Change injection site each time you inject.

D Do not inject into skin that is tender, damaged or has bruises or scars.

• 6. Prepare the injection site.

• Wash your hands.
• Clean skin with an alcohol wipe.

D Do not touch the injection site again before the injection.

Step B: Perform the injection – Perform Step B only after completing Step A “Get ready for an injection”

• 1. Pull off the needle cap.

• Hold the syringe in the middle of the syringe body with the needle pointing away from you.
• Keep your hand away from the plunger.

D Do not get rid of any air bubbles in the syringe.

D Do not pull off the needle cap until you are ready to inject.

D Do not put the needle cap back on.

• Slowly push the plunger down as far as it will go until the syringe is empty.

• 5. Before you remove the needle, check that the syringe is empty.

• Pull the needle out at the same angle it was injected.
• If you see any blood, press a cotton ball or gauze on the site.

D Do not rub your skin after the injection.

• 6. Put your used syringe and the cap into a puncture-resistant container right away after use.

• Always keep the container out of the sight and reach of children.

D Do not put the needle cap back on.

D Do not throw the used syringe in household waste.

D Do not recycle your used puncture-resistant container.

D Do not dispose of your used puncture-resistant container in your household waste unless your local guidelines permit this. Ask your doctor, pharmacist or nurse how to throw away the container.

Package leaflet: Information for the patient

Kevzara 150 mg solution for injection in pre-filled pen

Kevzara 200 mg solution for injection in pre-filled pen Sarilumab

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help 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 start using 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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

In addition to this leaflet, you will be given a patient alert card, which contains important safety information that you need before and during treatment with Kevzara.

What is in this leaflet

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

• 2. What you need to know before you use Kevzara

• 3. How to use Kevzara

• 4. Possible side effects

• 5. How to store Kevzara

• 6. Contents of the pack and other information

1. What Kevzara is and what it is used for

What Kevzara is

Kevzara contains the active substance sarilumab. It is a type of protein – called a “monoclonal antibody”.

What Kevzara is used for

Kevzara is used to treat adults with moderately to severely active rheumatoid arthritis if previous therapy did not work well enough or was not tolerated. Kevzara can be used alone or together with a medicine called methotrexate.

It may help you by:

• slowing down damage to joints
• improving your ability to perform daily activities.

How Kevzara works

• Kevzara attaches to another protein called interleukin-6 (IL-6) receptor and blocks its action.
• IL-6 plays a major role in the symptoms of rheumatoid arthritis such as pain, swollen joints, morning stiffness, and fatigue.

2. What you need to know before you use Kevzara

Do not use Kevzara:

• if you are allergic to sarilumab or any of the other ingredients of this medicine (listed in section 6).
• if you have an active severe infection.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse if:

• you have any infection or, you get a lot of infections. Kevzara can lower your body's ability to fight infection and this means it can make you more likely to get infections or make your infection worse.
• you have tuberculosis (TB), symptoms of TB (persistent cough, weight loss, listlessness, mild fever), or have been in close contact with someone with TB. Before you are given Kevzara, your doctor will check you for TB.
• you have had viral hepatitis or other liver disease. Before you use Kevzara, your doctor will do a blood test to check your liver function.
• you have had diverticulitis (a condition of the lower bowel) or ulcers in your stomach or intestines, or develop symptoms such as fever and stomach (abdominal) pain that does not go away.
• you have ever had any type of cancer.
• you have recently had any vaccination or are going to have a vaccination.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before using Kevzara.

You will have blood tests before you are given Kevzara. You will also have the tests during your treatment. This is to check if you have a low blood cell count, liver problems, or changes in your cholesterol levels.

Children and adolescents

Kevzara is not recommended in children and adolescents under 18 years of age.

Other medicines and Kevzara

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This is because Kevzara can affect the way some other medicines work. Also some other medicines can affect the way Kevzara works.

In particular, do not use Kevzara and tell your doctor or pharmacist if you are using:

• a group of medicines called “Janus kinase (JAK) inhibitors” (used for disease like rheumatoid arthritis and cancer)
• other biological medicines used in the treatment of rheumatoid arthritis.

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist.

Kevzara can affect the way some medicines work: this means the dose of other medicines may need changing. If you are using any of the following medicines, tell your doctor or pharmacist before using Kevzara:

• statins, used to reduce cholesterol level
• oral contraceptives
• theophylline, used to treat asthma
• warfarin, used to prevent blood clots

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist.

Pregnancy and breast-feeding

Talk to your doctor before using Kevzara if you are pregnant or breast feeding, think you may be pregnant or are planning to have a baby.

• Do not take Kevzara if you are pregnant – unless your doctor specifically recommends it.
• The effects of Kevzara on an unborn baby are not known.
• You and your doctor should decide if you should use Kevzara if you are breast-feeding.

Driving and using machines

The use of Kevzara is not expected to affect your ability to drive or use machines. However, if you are feeling tired or unwell after you use Kevzara, you should not drive or use machines.

3. How to use Kevzara

Treatment should be started by a doctor experienced in the diagnosis and treatment of rheumatoid arthritis. Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Kevzara is given as an injection under the skin (called “subcutaneous” injection).

The recommended dose is one 200 mg injection every two weeks.

• Your doctor may adjust the dose of your medicine based on results of blood tests.

Learning how to use the pre-filled pen

• Your doctor, pharmacist, or nurse will show you how to inject Kevzara. Following these instructions Kevzara can be self-injected or administered by a care-giver.
• Carefully follow the “Instructions for Use” provided in the carton.
• Use the pre-filled pen exactly as described in the “Instructions for Use”.

If you use more Kevzara than you should

If you have used more Kevzara than you should, talk to your doctor, pharmacist or nurse.

If you miss a dose of Kevzara

If it has been 3 days or less since the missed dose:

• inject your missed dose as soon as you can.
• then inject your next dose at your regular time.

If it has been 4 days or more, inject the next dose at your regular time. Do not inject a double dose to make up for a forgotten injection.

If you are unsure when to inject your next dose: ask your doctor, pharmacist or nurse for instructions.

If you stop using Kevzara

Do not stop using Kevzara without talking to your doctor.

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.

Serious side effect

Tell your doctor straight away if you think you have an infection (which may affect up to 1 in every 10 people). The symptoms may include fever, sweats, or chills.

Other side effects

Tell your doctor, pharmacist, or nurse if you notice any of the following side effects:

Very Common (may affect more than 1 in 10 people):

• Low white blood cell counts shown by blood tests

Common (may affect up to 1 in 10 people):

• infections in your sinuses or throat, blocked or runny nose and sore throat (“upper respiratory tract infection”)
• urinary tract infection
• cold sores (“oral herpes”)
• low platelet counts shown by blood tests
• high cholesterol, high triglycerides shown by blood tests
• abnormal liver function tests
• injection site reactions (including redness and itching)

Uncommon (may affect up to 1 in 100 people):

• infection of the lungs
• inflammation of the deep skin tissue
• diverticulitis (a disease affecting the gut often with stomach (abdominal) pain, nausea and vomiting, fever, and constipation, or less commonly diarrhoea)

Rare (may affect up to 1 in 1000 people):

• perforation in stomach or intestines (a hole that develops in the wall of the gut)

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 Kevzara

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 label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C).

• Do not freeze or heat the pen.
• Once taken out the refrigerator, do not store Kevzara above 25 °C.
• Write down the date of removal from the refrigerator in the space provided on the outer carton.
• Use the pen within 14 days after taking it out of the refrigerator or the insulated bag.
• Keep the pen in the original carton in order to protect it from light.

Do not use this medicine if the solution in the pen is cloudy, discoloured or contains particles, or if any part of the pre-filled pen looks damaged.

After use, put the pen into a puncture-resistant container. Always keep the container out of the sight and reach of children. Ask your doctor, pharmacist, or nurse how to throw away the container. Do not recycle the container.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Kevzara contains

• The active substance is sarilumab.
• The other ingredients are arginine, histidine, polysorbate 20, sucrose, and water for injections.

What Kevzara looks like and contents of the pack

Kevzara is a clear, colourless to pale yellow solution for injection that comes in a pre-filled pen.

Each pre-filled pen contains 1.14 ml of solution delivering one single dose. It is available in pack sizes of 1 or 2 or a multipack of 6 pre-filled pens (3 packs of 2).

Not all pack sizes may be marketed.

Kevzara is available as 150 mg or 200 mg pre-filled pens.

Marketing Authorisation Holder

sanofi-aventis groupe

54, rue La Boétie

F-75008 Paris

France

Manufacturer

Sanofi-Aventis Deutschland GmbH

Brüningstraße 50

Industriepark Höchst

65926 Frankfurt am Main

Germany

Genzyme Ireland Ltd

IDA Industrial Park

Old Kilmeaden Road

Waterford,

Ireland

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

Belgie/Belgiqu­e/Belgien Sanofi Belgium Tél/Tel: +32 (0)2 710 54 00 Btnrapua Swixx Biopharma EOOD Ten.: +359 (0)2 4942 480 Česká republika sanofi-aventis, s.r.o. Tel: +420 233 086 111 Danmark Sanofi A/S Tlf: +45 45 16 70 00 Deutschland Sanofi-Aventis Deutschland GmbH Telefon: 0800 04 36 996 Telefon aus dem Ausland: +49 69 305 70 13

Lietuva Swixx Biopharma UAB Tel: +370 5 236 91 40 Luxembourg/Lu­xemburg Sanofi Belgium Tel/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) Magyarorszag SANOFI-AVENTIS Zrt. Tel.: +36 1 505 0050 Malta Sanofi S.r.l. +39. 02 39394275 Nederland Genzyme Europe B.V. Tel: +31 20 245 4000

Eesti Swixx Biopharma OÜ Tel: +372 640 10 30	Norge sanofi-aventis Norge AS Tlf: +47 67 10 71 00
EXXàôa sanofi-aventis AEBE Tql: +30 210 900 16 00	Österreich sanofi-aventis GmbH Tel: +43 1 80 185 – 0
España sanofi-aventis, S.A. Tel: +34 93 485 94 00	Polska sanofi-aventis Sp. z o.o. Tel.: +48 22 280 00 00
France sanofi-aventis france Tél: 0 800 222 555 Appel depuis l’étranger : +33 1 57 63 23 23	Portugal Sanofi – Produtos Farmacéuticos, Lda Tel: +351 21 35 89 400
Hrvatska Swixx Biopharma d.o.o. Tel: +385 1 2078 500	Romania Sanofi Romania SRL Tel: +40 (0) 21 317 31 36
Ireland sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +353 (0) 1 403 56 00	Slovenija Swixx Biopharma d.o.o. Tel: +386 1 235 51 00
Ísland Vistor hf. Sími: +354 535 7000	Slovenská republika Swixx Biopharma s.r.o. Tel: +421 2 208 33 600
Italia Sanofi S.r.l. Tel: 800 13 12 12 (domande di tipo tecnico) 800 536389 (altre domande)	Suomi/Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300
Kùnpoç C.A. Papaellinas Ltd. Tnk +357 22 741741	Sverige Sanofi AB Tel: +46 (0)8 634 50 00
Latvija Swixx Biopharma SIA Tel: +371 6 616 47 50	United Kingdom Sanofi Tel: +44 (0) 845 372 7101

This leaflet was last revised in

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

Kevzara 150 mg solution for injection in a pre-filled pen sarilumab

Instructions for use

The parts of the Kevzara pre-filled pen are shown in this picture.

Important information

This device is a single-dose pre-filled pen (called “pen” in these instructions). It contains 150 mg of Kevzara for injection under the skin (subcutaneous injection) once every two weeks.

Ask your healthcare professional to show you the right way to use the pen before your first injection.

Do

S Read all of the instructions carefully before using a pen.

S Check that you have the correct medicine and the correct dose.

S Keep unused pens in the original carton and store in the refrigerator between 2°C and 8°C.

S Keep the carton in an insulated bag with an ice pack when travelling.

S Let the pen warm up to room temperature for at least 60 minutes before using.

S Use the pen within 14 days after taking it out of the refrigerator or insulated bag.

S Keep the pen out of the sight and reach of children.

Do not

D Do not use a pen if it has been damaged or the cap is missing or not attached.

D Do not remove the cap until just before you are ready to inject.

D Do not press or touch the yellow needle cover with your fingers.

D Do not try to put the cap back on a pen.

D Do not re-use the pen.

D Do not freeze or heat the pen.

O Once removed from the refrigerator, do not store the pen above 25°C.

D Do not expose the pen to direct sunlight.

D Do not inject through your clothes.

If you have any further questions, ask your doctor, pharmacist or nurse or call the sanofi number on the package leaflet.

Step A: Get ready for an injection

• 1. Prepare all the equipment you will need on a clean, flat working surface.

• You will need an alcohol wipe, a cotton ball or gauze, and a puncture-resistant container.
• Take one pen out of the packaging by holding the middle of the pen body. Keep the remaining pen in the carton in the refrigerator.

• 2. Look at the label.

• Check that you have the correct medicine and the correct dose.
• Check the expiry date (EXP), this is shown on the side of the pens.

D Do not use the pen if the date has passed.

• 3. Look at the window.

• Check that the liquid is clear and colourless to pale yellow.
• You may see an air bubble, this is normal.

D Do not inject if the liquid is cloudy, discoloured or contains particles.

D Do not use if the window is solid yellow.

• 4. Lay the pen on a flat surface and allow it to warm up to room temperature (<25°C) for at least 60 minutes.

• Using the pen at room temperature may make the injection more comfortable. D Do not use the pen if it has been out of the refrigerator for more than 14 days. D Do not heat the pen; let it warm up on its own.

D Do not expose the pen to direct sunlight.

• 5. Select the injection site.

• You can inject into your thigh or belly (abdomen) except for the 5 cm around your belly button (navel). If somebody else gives you the injection, you can also use the outer area of the upper arm.
• Change injection site each time you inject.

D Do not inject into skin that is tender, damaged or has bruises or scars.

• Injection sites

• 6. Prepare the injection site.

• Wash your hands.
• Clean skin with an alcohol wipe.

D Do not touch the injection site again before the injection.

Step B: Perform the injection – Perform Step B only after completing Step A “Get ready for an injection”

1. Twist or pull off the orange cap.

D Do not remove the cap until you are ready to inject.

D Do not press or touch the yellow needle cover with your fingers.

3. Press down and hold the pen firmly against your skin.

• There will be a “click” when the injection starts.

• 4. Keep holding the pen firmly against your skin.

• The window will start to turn yellow.
• The injection can take up to 15 seconds.

• 5. There will be a second click. Check to see if the entire window has turned yellow before you remove the pen.

• If you do not hear the second click, you should still check to see if the window has turned fully yellow.

X If the window does not turn fully yellow, do not give yourself a second dose without speaking to your healthcare provider.

• 6. Pull the pen away from your skin.

• If you see any blood, press a cotton ball or gauze on the site. D Do not rub your skin after the injection.

• 7. Put your used pen and the cap into a puncture-resistant container right away after use.

• Always keep the container out of the sight and reach of children.

D Do not put the cap back on.

D Do not throw the used pens in household waste.

D Do not recycle your used puncture-resistant container.

D Do not dispose of your used puncture-resistant container in your household waste unless your local guidelines permit this. Ask your doctor, pharmacist or nurse how to throw away the container.

Kevzara 200 mg solution for injection in a pre-filled pen sarilumab

Instructions for use

The parts of the Kevzara pre-filled pen are shown in this picture.

Important information

This device is a single-dose pre-filled pen (called “pen” in these instructions). It contains 200 mg of Kevzara for injection under the skin (subcutaneous injection) once every two weeks.

Ask your healthcare professional to show you the right way to use the pen before your first injection.

Do

S Read all of the instructions carefully before using a pen.

S Check that you have the correct medicine and the correct dose.

S Keep unused pens in the original carton and store in the refrigerator between 2°C and 8°C.

S Keep the carton in an insulated bag with an ice pack when travelling.

S Let the pen warm up to room temperature for at least 60 minutes before using.

S Use the pen within 14 days after taking it out of the refrigerator or insulated bag.

S Keep the pen out of the sight and reach of children.

Do not

D Do not use a pen if it has been damaged or the cap is missing or not attached.

D Do not remove the cap until just before you are ready to inject.

D Do not press or touch the yellow needle cover with your fingers.

D Do not try to put the cap back on a pen.

D Do not re-use the pen.

D Do not freeze or heat the pen.

O Once removed from the refrigerator, do not store the pen above 25°C.

D Do not expose the pen to direct sunlight.

D Do not inject through your clothes.

If you have any further questions, ask your doctor, pharmacist or nurse or call the sanofi number on the package leaflet.

Step A: Get ready for an injection

• 1. Prepare all the equipment you will need on a clean, flat working surface.

• You will need an alcohol wipe, a cotton ball or gauze, and a puncture-resistant container.
• Take one pen out of the packaging by holding the middle of the pen body. Keep the remaining pen in the carton in the refrigerator.

• 2. Look at the label.

• Check that you have the correct medicine and the correct dose.
• Check the expiry date (EXP), this is shown on the side of the pens.

D Do not use the pen if the date has passed.

3. Look at the window.

• Check that the liquid is clear and colourless to pale yellow.
• You may see an air bubble, this is normal.

D Do not inject if the liquid is cloudy, discoloured or contains particles.

D Do not use if the window is solid yellow.

• 4. Lay the pen on a flat surface and allow it to warm up to room temperature (<25°C) for at least 60 minutes.

• Using the pen at room temperature may make the injection more comfortable.

D Do not use the pen if it has been out of the refrigerator for more than 14 days.

D Do not heat the pen; let it warm up on its own.

D Do not expose the pen to direct sunlight.

• 5. Select the injection site.

• You can inject into your thigh or belly (abdomen) except for the 5 cm around your belly button (navel). If somebody else gives you the injection, you can also use the outer area of the upper arm.
• Change injection site each time you inject.

D Do not inject into skin that is tender, damaged or has bruises or scars.

Injection sites

• 6. Prepare the injection site.

• Wash your hands.
• Clean skin with an alcohol wipe.

D Do not touch the injection site again before the injection.

Step B: Perform the injection – Perform Step B only after completing Step A “Get ready for an injection”

• 1. Twist or pull off the orange cap.

D Do not remove the cap until you are ready to inject.

D Do not press or touch the yellow needle cover with your fingers.

D Do not put the cap back on.

• 2. Put the yellow needle cover on your skin at roughly a 90° angle.

• Make sure you can see the window.

• 3. Press down and hold the pen firmly against your skin.

• There will be a “click” when the injection starts.

• 4. Keep holding the pen firmly against your skin.

• The window will start to turn yellow.
• The injection can take up to 15 seconds.

• 5. There will be a second click. Check to see if the entire window has turned yellow before you remove the pen.

• If you do not hear the second click, you should still check to see if the window has turned fully yellow.

X If the window does not turn fully yellow, do not give yourself a second dose without speaking to your healthcare provider.

• 6. Pull the pen away from your skin.

• If you see any blood, press a cotton ball or gauze on the site. D Do not rub your skin after the injection.

• 7. Put your used pen and the cap into a puncture-resistant container right away after use.

• Always keep the container out of the sight and reach of children.

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for sarilumab, the scientific conclusions of CHMP are as follows:

In view of available data on leukopenia and diverticulitis from clinical trials and spontaneous reports, including in some cases with a close temporal relationship, a positive de-challenge and in view of a plausible mechanism of action, the PRAC considers a causal relationship between sarilumab and these adverse reactions can be established. The PRAC review concluded that the product information of products containing sarilumab should be amended accordingly.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for sarilumab the CHMP is of the opinion that the benefitrisk balance of the medicinal product(s) containing sarilumab is unchanged subject to the proposed changes to the product information.

The CHMP recommends that the terms of the marketing authorisation(s) should be varied.

103

cDMARDs in TARGET included MTX, sulfasalazine, leflunomide and hydroxychloroquine t p-value <0.01 for difference from placebo

p-value <0.001 for difference from placebo

tttp-value <0.0001 for difference from placebo

f Primary endpoint

NA=Not Applicable as TARGET was a 24-week study

^ Major clinical response = ACR70 for at least 24 consecutive weeks during the 52-week period