SYLVANT 100 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

SYLVANT 100 mg powder for concentrate for solution for infusion

siltuximab

This medicine is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on 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.
• 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.

Contents of the pack

1. What is SYLVANT and what is it used for

1. What you need to know before you use SYLVANT
2. How to use SYLVANT

1. Possible side effects

1. Storage of SYLVANT

1. Contents of the pack and other information

1. What is SYLVANT and what is it used for

What is SYLVANT

SYLVANT is a medicine that contains the active substance siltuximab.

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

What is SYLVANT used for

SYLVANT is used to treat multicentric Castleman's disease (MCD) in adult patients who are not infected with the human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8).

Multicentric Castleman's disease causes the formation of benign tumors (non-cancerous growths) in the lymph nodes of the body. The symptoms of this disease may include feeling tired, night sweats, tingling sensation, and loss of appetite.

How SYLVANT works

Patients with MCD produce too much IL-6, and it is thought that this contributes to the abnormal growth of certain cells in the lymph nodes. By binding to IL-6, siltuximab blocks its activity and slows down abnormal cell growth. This helps to reduce the size of the affected lymph nodes, which reduces the symptoms of the disease and can help you to carry out your normal daily activities.

2. What you need to know before you use 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

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

• You currently have an infection; this is because SYLVANT may reduce your ability to fight infections, so they may get worse.
• You are going to be vaccinated or need to be vaccinated in the near future – this is because some vaccines should not be given with SYLVANT.

• You have high levels of lipids in your blood (hypertriglyceridemia) – this is because SYLVANT may increase these levels. Your doctor may prescribe you medicines to correct this.
• You have a condition such as stomach ulcer or diverticulitis that may increase the risk of a tear in the stomach or intestine (gastrointestinal perforation). The symptoms of a tear include stomach pain that gets worse, feeling sick (nausea), change in bowel habits, and fever – if you experience any of these symptoms, contact your doctor immediately.

• You have liver disease or changes in liver function tests. Your doctor will monitor you and keep an eye on your liver function.

If any of the above applies to you (or if you are not sure), talk to your doctor, pharmacist, or nurse before you start using SYLVANT.

Allergic reactions

Tell your doctor immediately if you have a severe allergic reaction during or after the infusion. The symptoms include: difficulty breathing, chest tightness, wheezing, severe dizziness or fainting, 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 can be serious, such as pneumonia or sepsis (also called "blood poisoning").

If you experience any symptoms of infection during treatment with SYLVANT, tell your doctor immediately. The symptoms include: cough, flu-like symptoms, feeling unwell, hot or red skin, fever. Your doctor may stop your treatment with SYLVANT immediately.

Children and adolescents

The safety and efficacy of SYLVANT in this population are not known, therefore, SYLVANT should not be given to children or 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, which is used to treat asthma

• warfarin, a blood thinner

• ciclosporin, which is used during and after organ transplantation

• oral contraceptives, which are used to prevent pregnancy.

If any of the above applies to you (or if you are not sure), talk to your doctor or pharmacist before you start using SYLVANT.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.

• SYLVANT should not be used during pregnancy. It is not known if SYLVANT has harmful effects on the unborn baby or on the mother during pregnancy or breastfeeding.

• You should not become pregnant while you are being treated with SYLVANT and for 3 months after your treatment has finished. During this time, you must use effective contraceptive methods.

• In some cases, if you are pregnant and need treatment for MCD, your doctor may advise you that the benefit of using SYLVANT for your health outweighs the potential risks to the fetus, including an increased risk of infection and the use of certain vaccines in babies born to mothers exposed to SYLVANT during pregnancy.

It is not known if SYLVANT passes into breast milk. You and your doctor will decide whether you should continue to use SYLVANT or breastfeed, and stop using SYLVANT.

Driving and using machines

SYLVANT is unlikely to affect your ability to drive, ride a bicycle, or use any tools or machines.

3. How to use SYLVANT

Your doctor or nurse will only give you SYLVANT in a hospital or clinic.

• The recommended dose is 11 milligrams per kilogram of body weight, given once every 3 weeks.

• SYLVANT will be given to you as an "intravenous infusion" (through a drip into a vein, usually in your arm).

• It will be given slowly over a period of 1 hour.

• You will be monitored for side effects during the infusion of SYLVANT.

• You will receive treatment until you and your doctor agree that you will not benefit from further treatment.

If you are given too much SYLVANT

This medicine will be given to you by your doctor or nurse, so 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 immediately. The effects of overdose with SYLVANT are not known.

If you stop treatment with SYLVANT

You should not stop using SYLVANT without talking to 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 occur with this medicine.

Tell your doctor immediately if you experience any of the following side effects, as they may need to stop your treatment:

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

• severe allergic reaction – the symptoms may include: difficulty breathing, chest tightness, wheezing, severe dizziness or fainting, swelling of the lips or skin rash.

Other side effects are:

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

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

• decrease in the number of white blood cells (neutropenia)

• decrease in the number of platelets (thrombocytopenia)

• itching

• rash, itchy skin rash (eczema)

• high levels of lipids in the blood (hypertriglyceridemia)

• high levels of uric acid in the blood, which can cause gout

• abnormal kidney function tests

• swelling of the arms, legs, neck, or face

• high blood pressure

• respiratory infections – such as of the nose, sinuses, or throat

• urinary tract infection

• cold

• sore throat

• stomach pain or discomfort, constipation, diarrhea, heartburn, mouth ulcers (mouth pain), nausea, vomiting

• feeling dizzy

• headache

• joint pain, pain in the arm or leg

• weight gain.

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

• high levels of cholesterol in the blood

Reporting of side effects

If you experience 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 Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 the month shown.

Store in a refrigerator (2°C to 8°C). Do not freeze. Store in the original package to protect from light.

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

6. Contents of the pack and other information

What SYLVANT contains

• The active substance is siltuximab. Each single-use vial contains 100 mg of siltuximab. After reconstitution, the solution contains 20 mg of siltuximab per ml.

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

Appearance and packaging

• SYLVANT is presented as a glass vial containing a white powder for concentrate for solution for infusion (powder for concentrate).

• SYLVANT is presented in packs containing 1 vial.

Marketing authorisation holder

Recordati Netherlands B.V.

Beechavenue 54,

1119PW Schiphol-Rijk

Netherlands

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden

Netherlands

Date of last revision of this leaflet:07/2023.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu. There are also links to other web sites about rare diseases and orphan medicines.

--------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

This medicine is for single use only.

1. Use aseptic technique.

1. Calculate the dose, the total volume of reconstituted SYLVANT solution needed, and the number of vials needed. The recommended needle for preparation is 21-gauge, 1½ inches (38 mm). The infusion bags (250 ml) should contain 5% Dextrose and should be made of polyvinyl chloride (PVC), or polyolefin (PO), or polypropylene (PP), or polyethylene (PE). Alternatively, PE bottles can be used.

1. Allow the vial(s) of SYLVANT to reach room temperature (15°C to 25°C) for approximately 30 minutes. SYLVANT should be kept at room temperature during the entire preparation time. Each vial should be reconstituted with 5.2 ml of water for injection for single use only to obtain 20 mg/ml solution.

1. Gently swirl (DO NOT SHAKE OR VORTEX OR FORCEFULLY SWIRL) the reconstituted vials to help dissolve the powder. The contents should not be removed until the powder is completely dissolved. The powder should dissolve in less than 60 minutes. Inspect the vials for particulate matter and discoloration prior to dose preparation. Do not use if particulate matter or discoloration is observed.

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

1. The reconstituted solution should not be stored for more than 2 hours before addition to the infusion bag. The infusion should be completed within 6 hours after addition of the reconstituted solution to the infusion bag. Administer the diluted solution over a period of 1 hour using PVC, or polyurethane (PU), or PE-lined infusion sets, with an in-line polyethersulfone (PES) filter (0.2 microns). SYLVANT does not contain preservatives; therefore, any unused infusion solution should not be stored for later use.

1. No physical or biochemical compatibility studies have been conducted to evaluate the administration of SYLVANT with other medicines. SYLVANT infusion should not be administered with other drugs using the same intravenous line.

1. Disposal of unused medicine and all materials that have been in contact with it should be done in accordance with local regulations.

Traceability

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