InfoCons Consumer Protection informs you – Cablivi – Package Leaflet

Before anything else

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

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

Cablivi contains the active substance caplacizumab. It is used to treat an episode of acquired thrombotic thrombocytopenic purpura in adults and adolescents of 12 years of age and older weighing at least 40 kg. This is a rare blood clotting disorder in which clots form in small blood vessels. These clots can block blood vessels and damage the brain, heart, kidneys, or other organs.

Cablivi prevents the formation of these blood clots by stopping platelets in the blood from clumping together. By doing so, Cab livi reduces the risk of experiencing another episode of aTTP soon after the first.

⚠️ 2. What you need to know before you use Cablivi

Do not use Cablivi

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

Warnings and precautions

Tell your doctor if you:

• bleed excessively or experience unusual symptoms such as headache, shortness of breath, tiredness, or fainting which may indicate serious internal bleeding. Your doctor may ask you to stop the treatment. The doctor will say when you can start your treatment again .
• are using medici nes that prevent or treat blood clots such as warfarin , heparin, rivaroxaban, apixaban. Your doctor will de cide how you should be treated .
• are using anti -platelet agents such as aspirin , or low molecular weight heparin (which prevent blood clots). Your doctor will decide how you should be treated.
• have a bleeding disorder such as hae mophilia . Your doctor will de cide how you should be treated .
• have severely reduced liver function. Your doctor will de cide how you should be treated .
• are going to have an operation or dental treatment . Your doctor will decide i f it can be postponed or if you should stop Cablivi before your surgery or dental treatment .

Children and adolescents

Cablivi is not recommended for children under 12 years and below 40 kg body weight .

Other medicines and Cablivi

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Also tell your doctor if you are using a n anticoagulant medicine such as vitamin K antagonists , rivaroxaba n, or apixaba n which treat blood clots or anti -platelet agents, such as aspirin , or low molecular weigh t heparin which prevent blood clots.

Pregnancy and breast -feeding Tell your doctor if you are pregnant or plan to get pregnant. Use of Cablivi is not recommended during pregnancy.

Tell your doctor if you are breastfeeding. Your doctor will advise you whether to discontinue breastfeeding or not use Cablivi, considering the benefit of breastfeeding to the baby and the benefit of Cablivi to you.

Driving and using machines

Cablivi is not expected to influence the ability to drive or use machines.

Cablivi contains sodium

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

💊 3. How to use Cablivi

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Treatment with Cablivi is started by a doctor experienced in blood disorders.

The recommended treatment is

• first dose
• 1 vial injected into a vein by a healthcare professional
• the medicine will be given before starting plasma exchange .
• subsequent doses
• 1 vial once daily as a subcutaneous injection (under the skin of the belly )
• the subcutaneous injection will be given after each daily plasma exchange
• after the daily plasma exchange finishes , your treatment with Cablivi will continue for at least 30 days with injection of 1 vial once daily
• your doctor may ask you to continue daily treatment until the underlying signs of your disease are resolved .

Your doctor may decide that you or your caregiver may inject Cablivi. In this case, your doctor or healthcare provider will train you or your caregiver on how to use Cablivi.

Instructions for use The first injection of Cablivi into your vein must be given by a healthcare professional. Instructions for healthcare professionals on how to inject Cablivi into your vein are at the end of the leaflet.

For each injection, use a fresh kit package to prepare the injection solution. Do not try to inject Cablivi until you have been taught how to do so by a healthcare professional. Never use the kit for another injection .

Step 1 – Cleaning

• Wash your hands thoroughly with soap and water.
• Prepare a clean flat surface for plac ing the kit package .
• Make sure you have a disposal container at hand.

Step 2 – Before use

• Make sure the kit package is complete.
• Check the expiry date . Do not use if the expiry date has passed.
• Do not use the kit if the packaging or the items in it are damaged in any way.
• Place all components of the kit on the clean flat surface.
• If the kit was not stored at room temperature, allow the vial and the syringe to reach room temperature (15°C – 25°C) by letting them stand at room temperature for a few minutes . Do not warm them up in any other way.

Step 3 – Disinfect the rubber stopper

• Remove the plastic flip -off cap from the vial. Do not use the vial if the green plastic cap is missing.
• Clean the exposed rubber stopper using one of the alcohol pads provided and allow it to dry for a few seconds.
• After cleaning, do not touch the rubber stopper or allow it to touch any surface.

Step 4 – Attaching the adapter

• Take the packed vial adapter and remove the paper cover. Leave the adapter in its opened plastic packaging. Do not touch the adapter itself.
• Place the adapter over the vial, while keeping the adapter in its plastic packaging.
• Press down firmly until the adapter snaps into place, with the adapter spike going through the vial stopper. Leave the adapter attached to the vial, s till in its outer packaging.

Step 5 – Prepare the syringe

• Holding the syringe in your hand, break off the white cap with your other hand.
• Do not use the syringe if this white cap is missing, loose or damaged.
• Do not touch the syringe tip or allow it to come into contact with any surfaces.
• Place the syringe on the clean flat surface.

Step 6 – Connect syringe with adapter and vial

• Take the vial with the attached adapter.
• Remove the plastic packaging from the adapter by holding the vial with one hand, pressing the sides of the adapter packaging with your other hand, and then lifting the packaging upwards.

Take care that the adapter does not come away from the vial.

• Hold the adapter with the attached vial with one hand. Place the tip of the syringe on the connector part of the vial adapter.
• Gently lock the syringe onto the vial by turning it clockwise until resistance is felt.

32 Step 7 – Prepare the solution

• Keep the vial standing vertically on the surface with the syringe pointing downwards.
• Slowly push the syringe’s plunger down until the syringe is empty. Do not remove the syringe from the vial.
• With the syringe still connected to the vial adapter, gently swirl the vial with connected syringe until the powder is dissolved. Avoid foaming. Do not shake the vial.
• Allow the vial with connected syringe to stand on the surface for 5 minutes at room temperature to allow the solution to completely dissolve. The plunger may rise up by itself again – this is normal.
• Go to step 8 immediately after these 5 minutes.

Step 8 – Draw up solution

• Check the solution for particles. All powder must be dissolved and the solution must be clear.
• Slowly press the syringe’s plunger fully down.
• Turn the whole – vial, adapter and syringe – upside down.
• While keeping it vertical, slowly pull the plunger to transfer all the solution into the syringe. Do not shake it.

Step 9 – Prepare the syringe for administration

• Turn the whole – vial, adapter and syringe – right- side up (with the syringe at the top).

Disconnect the filled syringe from the adapter by holding the adapter in one hand and gently turning the syringe counter -clockwise.

• Put the vial and the attached adapter into the supplied disposal container.
• Do not touch the syringe tip or allow it to touch the surface. Place the syringe on the clean flat surface.

33 • Go to step 10 to inject caplacizumab under the skin of the belly. Instructions for healthcare professionals on how to inject Cablivi into your vein are at the end of the leaflet.

Step 10 – Attach the needle

• Unpack the needle by tearing the paper cover off the needle packaging and removing the needle with protective cap.
• Without removing the needle cap, attach the needle to the syringe by turning clockwise until resistance is felt.
• Pull back the needle safety shield.
• Check the content of the syringe . Do not use the medicine if you see any cloudiness, clumps or anything else that looks abnormal. Contact your doctor or nurse if this happens.

Step 11 – Prepare injection site for injection under the skin

• Select a suitable place (‘injection site’) on your belly for injection under your skin. Avoid the area around the belly button. Select a different injection site from the one you used on the previous day to help the skin to recover after the injection.
• Use the second alcohol pad to clean the injection site you have chosen.

Step 1 2 – Administration

• Carefully remove the needle protection cap from the needle and throw it away. Make sure the needle does not touch anything before the injection.
• Hold the syringe at eye level with the needle pointing upwards.
• Remove any air bubbles by tapping the side of the syringe with your finger to make the bubbles rise towards the tip. Then, slowly push the plunger until a small amount of liquid comes out of the needle.
• Gently pinch the cleaned skin between your thumb and forefinger to make a fold.

34 • H old this skin fold during the entire injection.

• Insert the full length of the needle into the skin fold at an angle as shown in the illustration.
• Press the plunger down as far as it goes.
• P ull out the needle at the same angle you inserted it. Do not rub the injection site.

St ep 13 – After administration

• Immediately after the injection, move the needle safety shield over the needle, until it clicks into place.
• P ut the syringe with the needle in a disposal container.

I f you use more Cablivi than you should An overdose is unlikely since one vial contains only a single dose. Tell your doctor if you think you have had an overdose .

I f you forget to use Cablivi If you miss a dose you should still take it if it is within 12 hours of the scheduled time. If more than 12 hours have passed since the dose should have been given, do not take the missed dose, but inject the next dose at the usual time.

I f you stop using Cablivi To get the most benefit from your treatment, it is important to use Cablivi as prescribed and for as long as your doctor tells you to use it . Please talk to your doctor before you stop the treatment bec ause stopping it too early can cause your condition to come back.

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

❗ 4. Possible side effects

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

C ontact your doctor immediately if any of the following serious side effects occur.

Long or excessive bleeding.

Your doctor may decide to keep you under closer observation or change your treat ment .

Side effects in a clinical study were reported with the following frequencies:

Very common, may affect more than 1 in 10 people

• bleeding gums
• fever
• tiredness
• headach e
• nosebleeds
• hives Common, may affect up to 1 in 10 people
• bleeding from eye
• vomiting blood
• blood in the stools
• black, tarry stools
• bleeding from the stomach
• bleeding ha emorrhoids
• rectal bleeding
• injection site reactions: rash, itching and bleeding
• bleeding in brain as evidenced by severe headache of rapid onset, vomiting , decreased level of consciousness , fever , sometimes seizures and neck stiffness or neck pain
• muscle pain
• stroke
• blood in urine
• excessive bleeding during periods
• vaginal bleeding
• coughing blood
• shortness of breath
• bruise

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

🌡️ 5. How to store Cablivi

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 and carton 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.

Cablivi may be stored at a temperature not above 25 °C for a single period of up to 2 months, but not beyond the expiry date. Do not return Cablivi to refrigerated storage after storage at room temperature.

Never expose to temperatures above 30 °C.

Do not use Cablivi if you notice any particulate matter or discolouration prior to administration.

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 Cablivi contains

• powder vial
• The active substance is caplacizumab.

Each vial contains 10 mg caplacizumab.

• The other ingredients are sucrose, citric acid anhydrous, trisodium citrate dihydrate ( see

section 2 “Cablivi contains sodium”) and polysorbate 80.

• pre-filled syringe The pre -filled syringe contains 1 mL water for injections.

What Cablivi looks like and contents of the pack

Cablivi is provided as:

• a white powder for solution for injection in a glass vial , and
• water for injections in a pre -filled syringe to dissolve the powder After dissolving the powder in the solvent, the solution is clear, colourless or slightly yellowish.

Cablivi is available in

• single pack s each containing 1 vial with caplacizumab powder , 1 pre -filled syringe with solvent, 1 vial adapter , 1 needle and 2 alcohol swabs
• multipacks each containing 7 single packs
• multidose packs each containing 7 vials with caplacizumab powder, 7 pre -filled syringes with solvent, 7 vial adapters, 7 needles and 14 alcohol swabs.

Not all pack sizes may be marketed .

Marketing Authorisation Holder and Manufacturer

Ablynx NV Technologiepark 21 9052 Zwijnaarde Belgium 37 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 04 36 996 Tel. aus dem Ausland: +49 69 305 70 13 Nederland Sanofi 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 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 S p. 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 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 536389 Suomi/Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300 38 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 United Kingdom (Northern Ireland) sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +44 (0) 800 035 2525 This leaflet was last revised in .

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

🩺 Information intended for healthcare professionals only

The intravenous bolus injection of Cablivi given at the start of the treatment must be administered by a health care professional. Preparing a dose of Cablivi for intravenous injection should be done in the same way as for a subcutaneous injection (see Instructions for Use, step 1 to 9, in section 3).

Cablivi can be intravenously administered by connecting the prepared syringe to standard Luer locks of intravenous lines or using a suitable needle. The line can be flushed with sodium chloride 9 mg/m L (0.9%) solution for injection .

📄 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 Cablivi (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/18/1305).

⚠️ 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.