B. PACKAGE LEAFLET

Package leaflet: Information for the patient

SYLVANT 100 mg powder for concentrate for solution for infusion

siltuximab

▼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 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

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

• 3. How SYLVANT is given

• 4. Possible side effects

• 5. How to store SYLVANT

• 6. Contents of the pack and other information

1. What SYLVANT is and what it is used for

What SYLVANT is

SYLVANT is a medicine that contains the active substance siltuximab.

Siltuximab is a monoclonal antibody (a specialised type of protein) that binds selectively to an antigen (a target protein) in the body called interleukin-6 (IL-6).

What SYLVANT is used for

SYLVANT is used to treat multicentric Castleman’s disease (MCD) in adult patients who do not have human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8) infection.

Multicentric Castleman’s disease causes benign tumours (non-cancerous growths) to develop in the lymph nodes in the body. Symptoms of this disease may include feeling tired, sweating at night, having a tingling feeling, and loss of appetite.

How SYLVANT works

Patients with MCD produce too much IL-6 and this is thought to contribute to the abnormal growth of certain cells in lymph nodes. By binding to IL-6, siltuximab blocks its activity and stops abnormal cell growth. This helps reduce the size of the affected lymph nodes, which reduces the symptoms of the illness and should help you carry out your normal daily tasks.

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

You should not be given SYLVANT if:

You are severely allergic to siltuximab or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you are given SYLVANT if:

• you have an infection at the moment – this is because SYLVANT may lower your ability to feel or fight infections, and infections may get worse.

you are due to have a vaccination or may need to have one in the near future – this is because some vaccines should not be given with SYLVANT.

you have high level of fats in your blood (hypertriglyce­ridaemia) – this is because SYLVANT may increase these levels. Your doctor may prescribe medicines to correct this.

you have a condition such as stomach ulcer or diverticulitis that may increase the risk of getting a tear in the stomach or gut (gastrointestinal perforation). Signs of such a tear developing include stomach pain getting worse, feeling sick (nausea), change in bowel habits and fever – if you get any of these, contact your doctor right away.

you have liver disease or changes that show up in blood tests of the liver. Your doctor will monitor you and your liver function.

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

Allergic reactions

Tell your doctor straight away if you have a severe allergic reaction during or after the infusion. Signs include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.

Infections

You may be more likely to get infections while you are being treated with SYLVANT.

These infections may be serious, such as pneumonia or blood poisoning (also called “sepsis”).

Tell your doctor straight away if you get any signs of infection during treatment with SYLVANT. Signs include: cough, flu-like symptoms, feeling unwell, red or hot skin, fever. Your doctor may stop your treatment with SYLVANT straight away.

Children and adolescents

It is not known if SYLVANT is safe and effective in this population, therefore SYLVANT should not be given to children and adolescents.

Other medicines and SYLVANT

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• theophylline, used to treat asthma
• warfarin, a blood thinner
• cyclosporin, used during and after organ transplants
• oral contraceptives, used to prevent pregnancy.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think that you might be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.

• SYLVANT is not recommended for use during pregnancy. It is not known if SYLVANT may affect the baby or a pregnant or breast-feeding woman.
• You must not become pregnant while you are being treated with SYLVANT and for 3 months after your treatment has finished. You should use effective methods of contraception during this time.
• In some cases, if you are pregnant and need treatment for MCD, your doctor may advise that the benefit of taking SYLVANT for your health outweighs the possible risks to your unborn baby, including increased risk of infection and use of certain vaccines in babies born to mothers exposed to SYLVANT while pregnant.
• It is not known if. SYLVANT passes into breast milk. You and your doctor should decide if you

will continue to take SYLVANT, or breast-feed and discontinue SYLVANT.

Driving and using machines

SYLVANT is not likely to affect your ability to drive, cycle, or use any tools or machines.

• 3. How SYLVANT is given

SYLVANT will be given to you by your doctor or nurse, in a hospital or clinic only.

• The recommended dose is 11 milligrams per kilogram of body weight, given once every

• 3 weeks.

• SYLVANT will be given as an “intravenous infusion” (a drip into a vein, usually in your arm).
• It will be given slowly over a period of 1 hour.
• During the infusion with SYLVANT, you will be monitored for side effects.
• You will receive treatment until you and your doctor agree that you will no longer benefit from the treatment.

If you are given more SYLVANT than you should

As this medicine will be given to you by your doctor or nurse, it is unlikely that you will be given too much. If you think you have been given too much SYLVANT, tell your doctor or nurse straight away. It is not known what the possible side effects could be from having too much SYLVANT.

If you stop treatment with SYLVANT

You should not stop using SYLVANT without discussing with your doctor first.

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 may happen with this medicine.

Tell your doctor straight away if you notice the following side effects, as he or she may need to stop your treatment:

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

• severe allergic reaction – the signs may include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.

Other side effects include:

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

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

• drop in the number of white blood cells (neutropenia)
• drop in the number of platelets (thrombocytopenia)
• itching
• rash, itchy skin rash (eczema)
• high fat levels in your blood (hypertriglyce­ridaemia)
• high level of ‚uric acid‘ in the blood, which may cause gout
• abnormal kidney function test
• swelling in the arms, legs, neck or face
• high blood pressure
• respiratory infections – such as of the nose, sinuses or throat
• urinary tract infection
• common cold
• sore throat
• stomach pain or discomfort, constipation, diarrhoea, heartburn, ulcers (sores) in the mouth, nausea, vomiting
• feeling dizzy
• headache
• joint pain, arm or leg pain
• weight gain.

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

• high level of cholesterol in the blood

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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 By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SYLVANT

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 – 8°C). Do not freeze. Store in the original package in order to protect from light.

Do not use if you see opaque or foreign particles and/or if the solution appears discoloured after reconstitution.

6. Contents of the pack and other information

What SYLVANT contains

• The active substance is siltuximab. Each single-use vial contains 100 mg siltuximab. After reconstitution the solution contains 20 mg siltuximab per mL.
• The other ingredients (excipients) are histidine, histidine hydrochloride monohydrate, polysorbate 80, and sucrose.

What SYLVANT looks like and contents of the pack

• SYLVANT is supplied as a glass vial containing a white powder for concentrate for solution for infusion (powder for concentrate).
• SYLVANT is available in packs containing 1 vial.

Marketing Authorisation Holder

EUSA Pharma (Netherlands) B.V.

Beechavenue 54

1119PW Schiphol-Rijk

Netherlands

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden The Netherlands

This leaflet was last revised in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: There are also links to other websites about rare diseases and treatments.

The following information is intended for healthcare professionals only:

This medicinal product is for single use only.

• 1. Use aseptic technique.

• 2. Calculate the dose, total volume of reconstituted SYLVANT solution required and the number of vials needed. The recommended needle for preparation is 21-gauge 1^ inch (38 mm).

Infusion bags (250 mL) must contain Dextrose 5% and must be made of polyvinyl chloride (PVC), or polyolefin (PO), or polypropylene (PP), or polyethylene (PE). Alternatively PE bottles may be used.

• 3. Allow vial(s) of SYLVANT to come to room temperature (15°C to 25°C) over approximately 30 minutes. SYLVANT should remain at room temperature for the duration of the preparation. Each vial should be reconstituted with 5.2 mL of single-use water for injections to yield a 20 mg/mL solution.

• 4. Gently swirl (DO NOT SHAKE OR VORTEX OR SWIRL VIGOROUSLY) the reconstituted vials to aid the dissolution of the powder. Do not remove contents until all of the powder has been completely dissolved. The powder should dissolve in less than 60 minutes. Inspect the vials for particulate matter and discolouration prior to dose preparation. Do not use if visibly opaque or if foreign particles and/or solution discolouration are present.

• 5. Dilute the total volume of the reconstituted solution dose to 250 mL with sterile Dextrose 5%, by withdrawing a volume equal to the volume of reconstituted SYLVANT from the Dextrose 5%, 250 mL bag. Slowly add the total volume of reconstituted SYLVANT solution to the 250 mL infusion bag. Gently mix.

• 6. The reconstituted solution should be kept for no more than 2 hours prior to addition into the intravenous bag. The infusion should be completed within 6 hours of the addition of the reconstituted solution to the infusion bag. Administer the diluted solution over a period of 1 hour using administration sets lined with PVC, or polyurethane (PU), or PE, containing a 0.2-micron inline polyethersulfone (PES) filter. SYLVANT does not contain preservatives; therefore do not store any unused portion of the infusion solution for re-use.

• 7. No physical biochemical compatibility studies have been conducted to evaluate the co-administration of SYLVANT with other medicinal products. Do not infuse SYLVANT concomitantly in the same intravenous line with other agents.

• 8. Any unused product or waste material should be disposed of in accordance with local requirements.

Traceability

In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.

Package leaflet: Information for the patient

SYLVANT 400 mg powder for concentrate for solution for infusion

siltuximab

▼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 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

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

• 3. How SYLVANT is given

• 4. Possible side effects

• 5. How to store SYLVANT

• 6. Contents of the pack and other information

1. What SYLVANT is and what it is used for

What SYLVANT is

SYLVANT is a medicine that contains the active substance siltuximab.

Siltuximab is a monoclonal antibody (a specialised type of protein) that binds selectively to an antigen (a target protein) in the body called interleukin-6 (IL-6).

What SYLVANT is used for

SYLVANT is used to treat multicentric Castleman’s disease (MCD) in adult patients who do not have human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8) infection.

Multicentric Castleman’s disease causes benign tumours (non-cancerous growths) to develop in the lymph nodes in the body. Symptoms of this disease may include feeling tired, sweating at night, having a tingling feeling, and loss of appetite.

How SYLVANT works

Patients with MCD produce too much IL-6 and this is thought to contribute to the abnormal growth of certain cells in lymph nodes. By binding to IL-6, siltuximab blocks its activity and stops abnormal cell growth. This helps reduce the size of the affected lymph nodes, which reduces the symptoms of the illness and should help you carry out your normal daily tasks.

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

You should not be given SYLVANT if:

You are severely allergic to siltuximab or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you are given SYLVANT if:

• you have an infection at the moment – this is because SYLVANT may lower your ability to feel or fight infections, and infections may get worse.
• you are due to have a vaccination or may need to have one in the near future – this is because some vaccines should not be given with SYLVANT.
• you have high level of fats in your blood (hypertriglyce­ridaemia) – this is because SYLVANT may increase these levels. Your doctor may prescribe medicines to correct this.
• you have a condition such as stomach ulcer or diverticulitis that may increase the risk of getting a tear in the stomach or gut (gastrointestinal perforation). Signs of such a tear developing include stomach pain getting worse, feeling sick (nausea), change in bowel habits and fever – if you get any of these, contact your doctor right away.
• you have liver disease or changes that show up in blood tests of the liver. Your doctor will monitor you and your liver function.

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

Allergic reactions

Tell your doctor straight away if you have a severe allergic reaction during or after the infusion. Signs include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.

Infections

You may be more likely to get infections while you are being treated with SYLVANT.

These infections may be serious, such as pneumonia or blood poisoning (also called “sepsis”).

Tell your doctor straight away if you get any signs of infection during treatment with SYLVANT. Signs include: cough, flu-like symptoms, feeling unwell, red or hot skin, fever. Your doctor may stop your treatment with SYLVANT straight away.

Children and adolescents

It is not known if SYLVANT is safe and effective in this population, therefore SYLVANT should not be given to children and adolescents.

Other medicines and SYLVANT

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• theophylline, used to treat asthma
• warfarin, a blood thinner
• cyclosporin, used during and after organ transplants
• oral contraceptives, used to prevent pregnancy.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think that you might be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.

• SYLVANT is not recommended for use during pregnancy. It is not known if SYLVANT may affect the baby or a pregnant or breast-feeding woman.
• You must not become pregnant while you are being treated with SYLVANT and for 3 months after your treatment has finished. You should use effective methods of contraception during this time.
• In some cases, if you are pregnant and need treatment for MCD, your doctor may advise that the benefit of taking SYLVANT for your health outweighs the possible risks to your unborn baby, including increased risk of infection and use of certain vaccines in babies born to mothers exposed to SYLVANT while pregnant.
• It is not known if. SYLVANT passes into breast milk. You and your doctor should decide if you will continue to take SYLVANT, or breast-feed and discontinue SYLVANT.

Driving and using machines

SYLVANT is not likely to affect your ability to drive, cycle, or use any tools or machines.

• 3. How SYLVANT is given

SYLVANT will be given to you by your doctor or nurse, in a hospital or clinic only.

• The recommended dose is 11 milligrams per kilogram of body weight, given once every

• 3 weeks.

• SYLVANT will be given as an “intravenous infusion” (a drip into a vein, usually in your arm).
• It will be given slowly over a period of 1 hour.
• During the infusion with SYLVANT, you will be monitored for side effects.
• You will receive treatment until you and your doctor agree that you will no longer benefit from the treatment.

If you are given more SYLVANT than you should

As this medicine will be given to you by your doctor or nurse, it is unlikely that you will be given too much. If you think you have been given too much SYLVANT, tell your doctor or nurse straight away. It is not known what the possible side effects could be from having too much SYLVANT.

If you stop treatment with SYLVANT

You should not stop using SYLVANT without discussing with your doctor first.

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 may happen with this medicine.

Tell your doctor straight away if you notice the following side effects, as he or she may need to stop your treatment:

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

• severe allergic reaction – the signs may include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.

Other side effects include:

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

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

• drop in the number of white blood cells (neutropenia)
• drop in the number of platelets (thrombocytopenia)
• itching
• rash, itchy skin rash (eczema)
• high fat levels in your blood (hypertriglyce­ridaemia)
• high level of ‚uric acid‘ in the blood, which may cause gout
• abnormal kidney function test
• swelling in the arms, legs, neck or face
• high blood pressure
• respiratory infections – such as of the nose, sinuses or throat
• urinary tract infection
• common cold
• sore throat
• stomach pain or discomfort, constipation, diarrhoea, heartburn, ulcers (sores) in the mouth, nausea, vomiting
• feeling dizzy
• headache
• joint pain, arm or leg pain
• weight gain.

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

• high level of cholesterol in the blood

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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 By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SYLVANT

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 – 8°C). Do not freeze. Store in the original package in order to protect from light.

Do not use if you see opaque or foreign particles and/or if the solution appears discoloured after reconstitution.

6. Contents of the pack and other information

What SYLVANT contains

• The active substance is siltuximab. Each single-use vial contains 400 mg siltuximab. After

reconstitution the solution contains 20 mg siltuximab per mL.

• The other ingredients (excipients) are histidine, histidine hydrochloride monohydrate, polysorbate 80, and sucrose.

What SYLVANT looks like and contents of the pack

• SYLVANT is supplied as a glass vial containing a white powder for concentrate for solution for infusion (powder for concentrate).
• SYLVANT is available in packs containing 1 vial.

Marketing Authorisation Holder

EUSA Pharma (Netherlands) B.V.

Beechavenue 54

1119PW Schiphol-Rijk

Netherlands

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden The Netherlands

This leaflet was last revised in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: There are also links to other websites about rare diseases and treatments.

The following information is intended for healthcare professionals only:

This medicinal product is for single use only.

• 1. Use aseptic technique.

• 2. Calculate the dose, total volume of reconstituted SYLVANT solution required and the number of vials needed. The recommended needle for preparation is 21-gauge 1^ inch (38 mm).

Infusion bags (250 mL) must contain Dextrose 5% and must be made of polyvinyl chloride (PVC), or polyolefin (PO), or polypropylene (PP), or polyethylene (PE). Alternatively PE bottles may be used.

• 3. Allow vial(s) of SYLVANT to come to room temperature (15°C to 25°C) over approximately 30 minutes. SYLVANT should remain at room temperature for the duration of the preparation. Each vial should be reconstituted with 5.2 mL of single-use water for injections to yield a 20 mg/mL solution.

• 4. Gently swirl (DO NOT SHAKE OR VORTEX OR SWIRL VIGOROUSLY) the reconstituted vials to aid the dissolution of the powder. Do not remove contents until all of the powder has been completely dissolved. The powder should dissolve in less than 60 minutes. Inspect the vials for particulate matter and discolouration prior to dose preparation. Do not use if visibly opaque or if foreign particles and/or solution discolouration are present.

• 5. Dilute the total volume of the reconstituted solution dose to 250 mL with sterile Dextrose 5%, by withdrawing a volume equal to the volume of reconstituted SYLVANT from the Dextrose 5%, 250 mL bag. Slowly add the total volume of reconstituted SYLVANT solution to the 250 mL infusion bag. Gently mix.

• 6. The reconstituted solution should be kept for no more than 2 hours prior to addition into the intravenous bag. The infusion should be completed within 6 hours of the addition of the reconstituted solution to the infusion bag. Administer the diluted solution over a period of 1 hour using administration sets lined with PVC, or polyurethane (PU), or PE, containing a 0.2-micron inline polyethersulfone (PES) filter. SYLVANT does not contain preservatives; therefore do not store any unused portion of the infusion solution for re-use.

• 7. No physical biochemical compatibility studies have been conducted to evaluate the co-administration of SYLVANT with other medicinal products. Do not infuse SYLVANT concomitantly in the same intravenous line with other agents.

• 8. Any unused product or waste material should be disposed of in accordance with local requirements.

Traceability

In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.

Package leaflet: Information for the patient

SYLVANT 400 mg powder for concentrate for solution for infusion

siltuximab

▼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 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

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

• 3. How SYLVANT is given

• 4. Possible side effects

• 5. How to store SYLVANT

• 6. Contents of the pack and other information

1. What SYLVANT is and what it is used for

What SYLVANT is

SYLVANT is a medicine that contains the active substance siltuximab.

Siltuximab is a monoclonal antibody (a specialised type of protein) that binds selectively to an antigen (a target protein) in the body called interleukin-6 (IL-6).

What SYLVANT is used for

SYLVANT is used to treat multicentric Castleman’s disease (MCD) in adult patients who do not have human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8) infection.

Multicentric Castleman’s disease causes benign tumours (non-cancerous growths) to develop in the lymph nodes in the body. Symptoms of this disease may include feeling tired, sweating at night, having a tingling feeling, and loss of appetite.

How SYLVANT works

Patients with MCD produce too much IL-6 and this is thought to contribute to the abnormal growth of certain cells in lymph nodes. By binding to IL-6, siltuximab blocks its activity and stops abnormal cell growth. This helps reduce the size of the affected lymph nodes, which reduces the symptoms of the illness and should help you carry out your normal daily tasks.

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

You should not be given SYLVANT if:

You are severely allergic to siltuximab or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you are given SYLVANT if:

• you have an infection at the moment – this is because SYLVANT may lower your ability to feel or fight infections, and infections may get worse.
• you are due to have a vaccination or may need to have one in the near future – this is because some vaccines should not be given with SYLVANT.
• you have high level of fats in your blood (hypertriglyce­ridaemia) – this is because SYLVANT may increase these levels. Your doctor may prescribe medicines to correct this.
• you have a condition such as stomach ulcer or diverticulitis that may increase the risk of getting a tear in the stomach or gut (gastrointestinal perforation). Signs of such a tear developing include stomach pain getting worse, feeling sick (nausea), change in bowel habits and fever – if you get any of these, contact your doctor right away.
• you have liver disease or changes that show up in blood tests of the liver. Your doctor will monitor you and your liver function.

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

Allergic reactions

Tell your doctor straight away if you have a severe allergic reaction during or after the infusion. Signs include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.

Infections

You may be more likely to get infections while you are being treated with SYLVANT.

These infections may be serious, such as pneumonia or blood poisoning (also called “sepsis”).

Tell your doctor straight away if you get any signs of infection during treatment with SYLVANT. Signs include: cough, flu-like symptoms, feeling unwell, red or hot skin, fever. Your doctor may stop your treatment with SYLVANT straight away.

Children and adolescents

It is not known if SYLVANT is safe and effective in this population, therefore SYLVANT should not be given to children and adolescents.

Other medicines and SYLVANT

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• theophylline, used to treat asthma
• warfarin, a blood thinner
• cyclosporin, used during and after organ transplants
• oral contraceptives, used to prevent pregnancy.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think that you might be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.

• SYLVANT is not recommended for use during pregnancy. It is not known if SYLVANT may affect the baby or a pregnant or breast-feeding woman.
• You must not become pregnant while you are being treated with SYLVANT and for 3 months after your treatment has finished. You should use effective methods of contraception during this time.
• In some cases, if you are pregnant and need treatment for MCD, your doctor may advise that the benefit of taking SYLVANT for your health outweighs the possible risks to your unborn baby, including increased risk of infection and use of certain vaccines in babies born to mothers exposed to SYLVANT while pregnant.
• It is not known if. SYLVANT passes into breast milk. You and your doctor should decide if you will continue to take SYLVANT, or breast-feed and discontinue SYLVANT.

Driving and using machines

SYLVANT is not likely to affect your ability to drive, cycle, or use any tools or machines.

• 3. How SYLVANT is given

SYLVANT will be given to you by your doctor or nurse, in a hospital or clinic only.

• The recommended dose is 11 milligrams per kilogram of body weight, given once every

• 3 weeks.

• SYLVANT will be given as an “intravenous infusion” (a drip into a vein, usually in your arm).
• It will be given slowly over a period of 1 hour.
• During the infusion with SYLVANT, you will be monitored for side effects.
• You will receive treatment until you and your doctor agree that you will no longer benefit from the treatment.

If you are given more SYLVANT than you should

As this medicine will be given to you by your doctor or nurse, it is unlikely that you will be given too much. If you think you have been given too much SYLVANT, tell your doctor or nurse straight away. It is not known what the possible side effects could be from having too much SYLVANT.

If you stop treatment with SYLVANT

You should not stop using SYLVANT without discussing with your doctor first.

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 may happen with this medicine.

Tell your doctor straight away if you notice the following side effects, as he or she may need to stop your treatment:

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

• severe allergic reaction – the signs may include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.

Other side effects include:

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

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

• drop in the number of white blood cells (neutropenia)
• drop in the number of platelets (thrombocytopenia)
• itching
• rash, itchy skin rash (eczema)
• high fat levels in your blood (hypertriglyce­ridaemia)
• high level of ‚uric acid‘ in the blood, which may cause gout
• abnormal kidney function test
• swelling in the arms, legs, neck or face
• high blood pressure
• respiratory infections – such as of the nose, sinuses or throat
• urinary tract infection
• common cold
• sore throat
• stomach pain or discomfort, constipation, diarrhoea, heartburn, ulcers (sores) in the mouth, nausea, vomiting
• feeling dizzy
• headache
• joint pain, arm or leg pain
• weight gain.

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

• high level of cholesterol in the blood

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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 By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SYLVANT

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 – 8°C). Do not freeze. Store in the original package in order to protect from light.

Do not use if you see opaque or foreign particles and/or if the solution appears discoloured after reconstitution.

6. Contents of the pack and other information

What SYLVANT contains

• The active substance is siltuximab. Each single-use vial contains 400 mg siltuximab. After

reconstitution the solution contains 20 mg siltuximab per mL.

• The other ingredients (excipients) are histidine, histidine hydrochloride monohydrate, polysorbate 80, and sucrose.

What SYLVANT looks like and contents of the pack

• SYLVANT is supplied as a glass vial containing a white powder for concentrate for solution for infusion (powder for concentrate).
• SYLVANT is available in packs containing 1 vial.

Marketing Authorisation Holder

EUSA Pharma (Netherlands) B.V.

Beechavenue 54

1119PW Schiphol-Rijk

Netherlands

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden

The Netherlands

This leaflet was last revised in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: There are also links to other websites about rare diseases and treatments.

The following information is intended for healthcare professionals only:

This medicinal product is for single use only.

• 1. Use aseptic technique.

• 2. Calculate the dose, total volume of reconstituted SYLVANT solution required and the number of vials needed. The recommended needle for preparation is 21-gauge 1^ inch (38 mm).

Infusion bags (250 mL) must contain Dextrose 5% and must be made of polyvinyl chloride (PVC), or polyolefin (PO), or polypropylene (PP), or polyethylene (PE). Alternatively PE bottles may be used.

• 3. Allow vial(s) of SYLVANT to come to room temperature (15°C to 25°C) over approximately 30 minutes. SYLVANT should remain at room temperature for the duration of the preparation. Each vial should be reconstituted with 20.0 mL of single-use water for injections to yield a 20 mg/mL solution.

• 4. Gently swirl (DO NOT SHAKE OR VORTEX OR SWIRL VIGOROUSLY) the reconstituted vials to aid the dissolution of the powder. Do not remove contents until all of the powder has been completely dissolved. The powder should dissolve in less than 60 minutes. Inspect the vials for particulate matter and discolouration prior to dose preparation. Do not use if visibly opaque or if foreign particles and/or solution discolouration are present.

• 5. Dilute the total volume of the reconstituted solution dose to 250 mL with sterile Dextrose 5%, by withdrawing a volume equal to the volume of reconstituted SYLVANT from the Dextrose 5%, 250 mL bag. Slowly add the total volume of reconstituted SYLVANT solution to the 250 mL infusion bag. Gently mix.

• 6. The reconstituted solution should be kept for no more than 2 hours prior to addition into the intravenous bag. The infusion should be completed within 6 hours of the addition of the reconstituted solution to the infusion bag. Administer the diluted solution over a period of 1 hour using administration sets lined with PVC, or polyurethane (PU), or PE, containing a 0.2-micron inline polyethersulfone (PES) filter. SYLVANT does not contain preservatives; therefore do not store any unused portion of the infusion solution for re-use.

• 7. No physical biochemical compatibility studies have been conducted to evaluate the co-administration of SYLVANT with other medicinal products. Do not infuse SYLVANT concomitantly in the same intravenous line with other agents.

• 8. Any unused product or waste material should be disposed of in accordance with local requirements.