InfoCons Consumer Protection informs you – Teizeild – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start taking 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, nurse or pharmacist .
• If you get any side effects, talk to your doctor, nurse or pharmacist . This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What Teizeild is and what it is used for

Teizeild is a medicine that contains the active substance teplizumab. Teplizumab is a monoclonal antibod y, a type of protein designed to recognise and attach to a target.

Teizeild is used in adults and children 8 years of age and older who have stage 2 type 1 diabetes (T1D) . It is used to delay the onset of stage 3 T1D in these patients .

Type 1 diabetes (T1D) is a n autoimmune condition that occurs when your own immune system (the body’s natural defences) mistakenly attacks cells in the pancreas ( called beta cells ) that make insulin (a hormone that controls the amount of glucose ( sugar ) in the blood ). Over time, this leads to a complete lack of insulin in the body.

T1D develops in three stages. In stage 1 T1D, your blood sugar levels are normal and you don’t have any symptoms . In stage 2 T1D, your blood sugar levels start to increase and become abnormal . In stage 3 T1D, you r body can not make enough insulin on its ow n to control your blood sugar and you need insulin treatment to manage the condition.

Before starting treatment with Teizeild your doctor will confirm that you have stage 2 T1D by ensuring that you test positive for 2 or more autoantibodies (a type of protein made by the immune system indicating the autoimmune destruction of beta cells in the pancreas ) and have dysglycaemia without persistently high blood sugar levels (overt hyperglycaemia) .

The active substance in Teizeild , teplizumab, binds to an activating molecule on the surface of T cells (a type of white blood cell) known as CD3. By binding to CD3, teplizumab deactivates the T cells that attack and destroy beta cells which helps to preserv e beta cell function and slows down the progression of T1D .

If you have any questions on how Teizeild works or about your treatment with Teizeild , ask your doctor, nurse or pharmacist.

⚠️ 2. What you need to know before you are given Teizeild

You must not be given Teizeild

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

Warnings and precautions

Talk to your doctor, nurse or pharmacist about all your medical conditions before you are given Teizeild , including if you:

• have a serious infection – or an infection that does not go away or that keeps coming back.
• have recently had or are planning to have a vaccine. Teizeild may affect how well a vaccine works. Tell your doctor, nurse or pharmacist that you are being treated with Teizeild before having a vaccine. Depending on the type of vaccine, your doctor will tell you when you can safely receive any vaccine prior to and after the treatment with Teizeild .

After you have been given Teizeild Tell your doctor or nurse immediately if you have any of the following:

• Fever, nausea, tiredness, headache, muscle pain (myalgia) , joint pain (a rthralgia) or increased liver enzymes in your blood, which may be signs and symptoms of a serious condition known as cytokine release syndrome (see section 4 “Possible side effects”) .
• Fever, chills , tiredness, nausea, vomiting, cough, shortness of breath, chest pain, swollen lymph nodes or a painful, swollen lump that feels warm (ab scess). These may be symptoms of an infection (see section 4 “Possible side effects”) .
• Hives, rash, joint pain or swelling, itching, dizziness, wheezing, difficulty breathing or swelling of your tongue and lips. These may be symptoms of allergic reactions (see section 4 “Possible side effects”) .

Teizeild may lower your lymphocyte count, a type of white blood cells that helps fight infections (see section 4 “Possible side effects”) .

Your doctor will do blood tests to check your liver and your complete blood counts before you start treatment and during treatment with Teizeild .

Patient Guide Your doctor will provide you with a patient guide that includes information about possible side effects, their symptoms, and instructions on what to do if they occur. Read it carefully and ask your doctor if you have any questions about your treatment.

Children

The safety and efficacy of Teizeild in children under 8 years of age have not been established.

Other medicines and Teizeild

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

Pregnancy and breast -feeding Tell your doctor, nurse or pharmacist if you are pregnant , think you may be pregnant or are planning to have a baby . Teizeild may harm your unborn baby.

• Teizeild is not recommended during pregnancy and in women who can have children who are not using contraception (birth control) .

Tell your doctor, nurse or pharmacist if you are breast -feeding or are planning to breast -feed. It is not known if Teizeild passes into your breast milk and if it can harm your baby.

29 • It is recommended to stop breast -feeding during treatment with Teizeild and for 30 days after the last dose .

Driving and using machines

Teizeild has minor effects on your ability to drive and use machines. If you feel tired (fatigue) (see section 4 “Possible side effects”) , do not drive or use machines before discussing it with your doctor, nurse or pharmacist .

Teizeild contains sodium and polysorbate 80

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium – free’.

This medicine contains 0.10 mg of polysorbate 80 in each vial which is equivalent to 0.05 mg/mL.

Polysorbates may cause allergic reactions. Tell your doctor if you or your child have any known allergies.

💊 3. How Teizeild is given

Teizeild should be given to you by a healthcare professional with access to appropriate medical support needed to manage serious side effects . Teizeild is given as an infusion (drip) into a vein (intravenous (IV)).

Your doctor will determine your dose of Teizeild based on your body surface area , which is a way of measuring the total area of your skin .

How often Teizeild is given You will be given the infusion once a day for 14 days. Each infusion will last a minimum of 30 minutes.

For the first 5 days of treatment, your doctor or nurse will give you other medicines by mouth to reduce your risk of developing cytokine release syndrome.

These medicines include:

• ibuprofen or naproxen – or other medicines for fever such as paracetamol
• an antihistamine – a medicine used to treat allergies
• an anti -nausea medicine.

If you are given more Teizeild than you should

If you are given too much Teizeild , your doctor will treat and monitor any side effects you may have .

If you miss a Teizeild infusion If you miss a scheduled infusion, your doctor or nurse will continue your treatment on the next scheduled day. You will not get 2 infusions on the same day.

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

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During and after your treatment with Teizeild , your doctor or nurse will check for serious side effects, as well as other side effects, and treat you as needed.

30 Serious side effects Tell your doctor or nurse immediately if you have any of the following serious side effects:

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

Decrease in lymphocytes (a type of white blood cells) , as measured in blood tests.

• This can happen after your first dose.
• This can affect how well your body can fight infections.
• Longer and more severe decreases in lymphocytes could make you more susceptible to infections (see section 2 “What you need to know before you are given Teizeild ”).
• Your lymphocytes counts should start to go back to normal after your fifth dose of Teizeild .

Common (may affect up to 1 in 10 people)

Cytokine release syndrome (CRS) The signs and symptoms may start during the first 5 days of treatment and may include:

• fever
• feeling tired
• muscle and joint pain
• nausea
• headache
• increased liver enzymes and bilirubin (a breakdown product of red blood cells) in your blood.

Uncommon (may affect up to 1 in 100 people )

• Infections , with symptoms such as fever, chills, tiredness, nausea, vomiting, cough, shortness of breath, chest pain, swollen lymph nodes or a painful, swollen lump that feels warm (abscess)
• Hypersensitivity , with symptoms such as hives, rash, joint pain or swelling, itching, dizziness, wheezing, difficulty breathing or swelling of your tongue and lips .

Other side effects

Tell your doctor or nurse if you have any of the following side effects:

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

• Low levels of blood platelets , components that help the blood to clot (thrombocytopenia)
• Low levels of neutrophils, a type of white blood cell (neutropenia)
• Low levels of white blood cells (leucopenia)
• Decrease in haemoglobin ( the protein in red blood cells that carries oxygen around the body )
• Headache
• Vomiting
• Nausea
• Increase in liver enzyme levels
• Rash
• Itching (prurit us)
• Fever (pyrexia)
• Feeling tired (fatigue)

Common (may affect up to 1 in 10 people)

• Increased levels of eosinophil s, a type of white blood cell (eosinophilia )
• Diarrhoea
• Abdominal (belly) pain
• Increase in bilirubin levels
• Itchy skin 31 • Red and itchy raised bumps (hives)
• Skin exfoliation
• Chills

Not known (frequency cannot be estimated from the available data)

• Mononucleosis (Epstein -Barr virus) reactivation
• Pain
• Illness Your doctor or nurse may pause or stop your treatment if you get liver problems, have a serious infection, or if your blood counts stay too low .

Reporting of side effects

If you get any side effects, talk to your doctor, nurse 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. How to store Teizeild

Your doctor, pharmacist or nurse is responsible for storing this medicine and disposing of any unused product correctly. The following information is intended for healthcare professionals.

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

Do not use this medicine after the expiry date which is stated on the carton and the vial 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 the vials.

Keep the vial in the outer carton in order to protect from light.

Store upright.

After dilution IV infusion bags Chemical , physical and microbial in-use stability has been demonstrated for 6 hours at ambient temperature (15 C to 25 C).

From a microbiological point of view, it is recommended that the product should be used immediately.

If not used immediately, in -use storage times and conditions prior to use are the responsibility of the user and should not be longer than 6 hours at ambient temperature (15 C to 25 C).

Syringe -based infusions Chemical , physical and microbial in-use stability has been demonstrated for 12 hours under refrigerated conditions (2 C to 8 C), followed by no more than 6 hours at ambient temperature (15 C to 25 C).

From a microbiological point of view, it is recommended that the product should be used immediately.

If not used immediately, in -use storage times and conditions prior to use are the responsibility of the user and should not be longer than 12 hours under refrigerated conditions (2 C to 8 C), followed by no more than 6 hours at ambient temperature (15 C to 25 C).

Do not throw away medicines via wastewater or household waste. Ask your doctor or nurse 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 Teizeild contains

• The active substance is teplizumab
• One vial contains 2 mg of teplizumab
• The other ingredients (excipients) are dibasic sodium phosphate, monobasic sodium phosphate, polysorbate 80 (E 433), sodium chloride, and water for injection s (see section 2 “Teizeild contains sodium and polysorbate 80” ).

What Teizeild looks like and contents of the pack

Teizeild is a concentrate for solution for infusion in a vial ( 1 mg/mL). It is a clear, colourless solution.

Teizeild is supplied in a carton pack containing 1, 10 or 14 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Sanofi Winthrop Industrie 82 avenue Raspail 94250 Gentilly France

Manufacturer

Sanofi B.V.

Paasheuvelweg 25 1105 BP Amsterdam Netherlands For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Sanofi Belgium Tél/Tel: +32 (0)2 710 54 00 Lietuva Swixx Biopharma UAB Tel: +370 5 236 91 40 България Swixx Biopharma EOOD Тел.: +359 (0)2 4942 480 Luxembourg/Luxemburg Sanofi Belgium Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) Česká republika Sanofi s.r.o.

Tel: +420 233 086 111 Magyarország SANOFI -AVENTIS Zrt.

Tel.: +36 1 505 0050 Danmark Sanofi A/S Tlf.: +45 45 16 70 00 Malta Sanofi S.r.l.

Tel: +39 02 39394275 Deutschland Sanofi -Aventis Deutschland GmbH Tel.: 0800 52 52 010 Tel. aus dem Ausland: +49 69 305 21 131 Nederland Sanofi B.V.

Tel: +31 20 245 4000 33 Eesti Swixx Biopharma OÜ Tel: +372 640 10 30 Norge sanofi -aventis Norge AS Tlf: +47 67 10 71 00 Ελλάδα Sanofi -Aventis Μονοπρόσωπη AEBE Τηλ: +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 Sp. z o.o.

Tel.: +48 22 280 00 00 France Sanofi Winthrop Industrie Tél: 0 800 222 555 Appel depuis l’étranger : +33 1 57 63 23 23 Portugal Sanofi – Produtos Farmacêuticos, Lda.

Tel: +351 21 35 89 400 Hrvatska Swixx Biopharma d.o.o.

Tel: +385 1 2078 500 România 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 ehf.

Sími: +354 535 7000 Slovenská republika Swixx Biopharma s.r.o.

Tel: +421 2 208 33 600 Italia Sanofi S.r.l.

Tel: 800 536389 Suomi/Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300 Κύπρος C.A. Papaellinas Ltd.

Τηλ: +357 22 741741 Sverige Sanofi AB Tel: +46 (0)8 634 50 00 Latvija Swixx Biopharma SIA Tel: +371 6 616 47 50

This leaflet was last revised i n

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu . ——————————————————————————————— —————————

🩺 Information intended for healthcare professionals only

Preparation for intravenous administration

• Must dilute Teizeild prior to use. This requires a two -step dilution process.

34 • In preparation for dilution, inspect the vial visually before use (the solution should be clear and colourless). Do not use if particulate matter or colouration is seen.

• Prepare using aseptic technique. Each vial is intended for single dose only.
• Start the infusion immediately after dilution. If not used immediately, store the diluted solution for infusion (see package leaflet, section “How to store Teizeild”).

Step 1: Initial dilution (1:10)

• Prepare 18 mL of sodium chloride 9 mg/mL (0.9%) solution for injection in a: o Sterile glass vial or o Sterile p olyvinylchloride (PVC) with di -(2-ethylhexyl)phthalate (DEHP) infusion bag or o Sterile syringe (polypropylene (PP), polycarbonate (PC) or glass)
• Remove the cap from the vial – this is the preparation start time.

Based on BSA dosing requirements (e.g. > 1.94 m2), two ( 2) Teizeild vials may be needed for days 5 through 14.

In this case, to make sure the complete dose for each day is contained in one ( 1) infusion bag or syringe : o Prepare two ( 2) dilution solutions o Add the cumulative volume for the calculated dose to a single infusion bag or syringe

• Remove 2 mL of Teizeild from the vial and slowly add to the 18 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. Mix gently by slowly swirling the vial or rocking the infusion bag or syringe . The resulting 20 mL diluted solution contains 100 micrograms (mcg)/mL of teplizumab.
• Calculate patient’s BSA (e.g. using the Mosteller formula ) before treatment.
• Using the patient’s BSA, calculate the dose based on treatment day (see section 4.2).

Dose (x mcg )=Daily dosage level (x mcg m2)x BSA (m2)

• Calculate the volume of 100 mcg/mL Teizeild solution (prepared in Step 1) to be further diluted in Step 2.

Volume of initial dilution, 1:10 (mL) =Dose (x mcg) Step 2: Final dilution There are two different methods for intravenous administration of final dilution: infusion bag or syringe pump infusion. Use the appropriate calculation depending on the selected method.

• Infusion ba g for intravenous administration : o Using an appropriately sized syringe (e.g. 5 mL), withdraw the volume of diluted solution required for that day’s calculated dose from the 100 mcg/mL solution (see Step 1: Initial dilution (1:10)). o Slowly add contents of the syringe containing the dose to a PVC with DEHP infusion bag containing 25 mL sodium chloride 9 mg/mL (0.9%) solution for injection. Gently rock the infusion bag to ensure that the solution mixes sufficiently. Do not shake. o Infusion administration has a minimum duration of 30 minutes. Rate may be slowed for patient’s tolerability.
• Syringe (PP, PC or glass) for intravenous infusion via syringe pump [Concentration range 15 mcg/mL to 60 mcg/mL] : o Calculate th e maximum volume that can be administrated for the calculated dose (based on treatment day, dose and patient BSA) using a minimum infusion concentration of 15 mcg/mL.

Volume Infusion (mL) = Dose (x mcg) Minimum infusion concentration 15 mcg/mL o Calculate the volume of saline to be added to the infusion syringe: a) If the calculated maximum volume to be administered is ≤ 60 mL:

Volume Saline (mL) = Volume Infusion (mL) – Volume initial dilution, 1:10 (mL) b) If the calculated maximum volume to be administered exceeds 60 mL – the maximum infusion volume is capped at 60 mL.

Volume Saline (mL) = 60 mL – Volume initial dilution, 1:10 (mL) o Measure the appropriate volume of saline and transfer it to the infusion syringe. o Using an appropriately sized syringe (e.g. 5 mL), withdraw the volume of diluted Teizeild solution calculated above (see volume of initial dilution, 1:10) and add it to the infusion syringe. o Gently rock the infusion syringe to ensure that the solution mixes sufficiently. Do not shake. o Attach infusion syringe to a syringe pump. The syringe pump should support rates as low as 1 mL/hour. o Run infusion with syringe pump – do not manually push the syringe . Calculate the infusion rate (to ensure a minimum of 30 minutes). The maximum infusion rate should be 36 2 mL/min (maximum 120 mL/hour). The actual rate will vary based on the volume of infusion , as shown below.

Infusion rate (mL/minute) = Volume Infusion (mL) 30 minutes o Infusion administration has a minimum duration of 30 minutes. Rate may be slowed for patient’s tolerability.

These steps may be followed if using a sterile glass vial for dilution preparation instead of a syringe (for intravenous infusion via syringe pump). An overfill should be considered as part of the calculations.

Disposal The unused portion of remaining diluted Teizeild solution in the PVC with DEHP infusion bag, syringe or sterile glass vial should be discarded .

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

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Teizeild (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/25/1998).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.