Cablivi 10 mg powder and solvent for solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

Cablivi 10 mg powder and solvent for injectable solution

caplacizumab

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only; do not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet Contents

1. What Cablivi is and what it is used for
2. What you need to know before using Cablivi
3. How to use Cablivi
4. Possible adverse effects
5. How to store Cablivi
6. Contents of the pack and other information

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 (aTTP) in adults and adolescents aged 12 years and older who weigh 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 inhibiting blood platelets from clumping together. In this way, Cablivi reduces the risk of experiencing another episode of acquired thrombotic thrombocytopenic purpura (aTTP) shortly after the first episode.

2. What you need to know before using Cablivi

Do not use Cablivi

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

Warnings and precautions

Tell your doctor if:

• you are bleeding excessively or experience unusual symptoms such as headache, difficulty breathing, fatigue, or fainting, which may indicate serious internal bleeding. Your doctor may ask you to stop treatment. Your doctor will tell you when you can restart treatment.
• you are taking medicines used to prevent or treat blood clots, such as warfarin, heparin, rivaroxaban, or apixaban. Your doctor will decide how to manage your treatment.
• you are taking antiplatelet agents such as aspirin or low molecular weight heparin (which prevent blood clots). Your doctor will decide how to manage your treatment.
• you have a bleeding disorder, such as haemophilia. Your doctor will decide how to manage your treatment.
• you have severely impaired liver function. Your doctor will decide how to manage your treatment.
• you are scheduled for surgery or dental treatment. Your doctor will decide whether the procedure can be postponed or whether Cablivi should be stopped before surgery or dental treatment.

Children and adolescents

Cablivi is not recommended for children under 12 years of age and weighing less than 40 kg.

Other medicines and Cablivi

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

Also inform your doctor if you are taking anticoagulant medicines such as vitamin K antagonists, rivaroxaban, or apixaban, for the treatment of blood clots, or antiplatelet agents such as aspirin or low molecular weight heparin, which prevent blood clots.

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or planning to become pregnant. 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, taking into account the benefit of breastfeeding for the baby and the benefit of Cablivi for you.

Driving and using machines

Cablivi is not expected to affect the ability to drive or operate machinery.

Cablivi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; i.e., essentially "sodium-free".

3. How to use Cablivi

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Treatment with Cablivi must be initiated 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 administered before starting plasma exchange.

• subsequent doses

• 1 vial once daily as a subcutaneous injection (under the skin of the abdomen)

• the subcutaneous injection will be given after each daily plasma exchange

• after daily plasma exchange ends, treatment with Cablivi will continue for at least 30 days with one 1-vial injection per day

• your doctor may instruct you to continue daily treatment until the underlying signs of your disease have resolved.

Your doctor may decide that you or your caregiver may administer the Cablivi injection. In this case, your doctor or healthcare professional will train you or your caregiver on how to use Cablivi.

Instructions for use

The first intravenous injection of Cablivi must be administered by a healthcare professional. Instructions for healthcare professionals on how to inject Cablivi intravenously are located at the end of this leaflet.

For each injection, use a new pack to prepare the injection solution. Do not attempt to administer the Cablivi injection until a healthcare professional has shown you how to do so. Never use the contents of a pack for another injection.

Step 1 – Cleaning

• Wash your hands thoroughly with water and soap.
• Prepare a clean, flat surface to place the pack contents.
• Make sure you have a sharps container ready.

Step 2 – Before use

• Ensure the pack is complete.
• Check the expiry date. Do not use after the expiry date.
• Do not use the pack if any of its components are damaged in any way.
• Place all pack components on the clean, flat surface.
• If the pack has not been stored at room temperature, allow the vial and syringe to reach room temperature (15 °C – 25 °C) by leaving them at room temperature for several minutes. Do not heat them in any other way.

Step 3 – Disinfection of the rubber stopper

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

Step 4 – Attaching the adapter

• Take the vial adapter in its packaging and remove the paper cover. Leave the adapter in its open plastic container. Do not touch the adapter.

• Place the adapter onto the vial while keeping the adapter in its plastic container.
• Press firmly downward until the adapter clicks into place, with the adapter's tip piercing the vial stopper. Leave the adapter attached to the vial, still in its outer container.

Step 5 – Preparing the syringe

• Holding the syringe in one hand, break off the white cap with the other hand.
• Do not use the syringe if the white cap is missing, loose, or damaged.

• Do not touch the syringe tip or allow it to contact any surface.
• Place the syringe on the clean, flat surface.

Step 6 – Connecting the syringe to the adapter and vial

• Take the vial with the attached adapter.
• Remove the plastic container from the adapter by holding the vial with one hand, pressing the sides of the adapter container with the other hand, and then lifting the container upward. Be careful not to dislodge the adapter from the vial.

• Hold the adapter with the vial attached in one hand. Place the syringe tip into the connector part of the vial adapter.
• Securely attach the syringe to the vial by turning it clockwise until resistance is felt.

Step 7 – Preparing the solution

• Keep the vial upright on the surface with the syringe pointing downward.
• Slowly push the syringe plunger all the way down until the syringe is empty. Do not remove the syringe from the vial.
• With the syringe still attached to the vial adapter, gently rotate the vial with the syringe attached until the powder is completely dissolved. Avoid foaming. Do not shake the vial.

• Leave the vial with the syringe attached on the surface for 5 minutes at room temperature to allow the solution to fully dissolve. The plunger may rise back up on its own; this is normal.
• Proceed immediately to Step 8 after these 5 minutes.

Step 8 – Withdrawing the solution

• Check the solution for particles. All powder should be dissolved and the solution should be clear.
• Slowly press the syringe plunger fully down.
• Turn the vial, adapter, and syringe completely upside down.
• While holding it upright, slowly pull back the plunger to draw all the solution into the syringe. Do not shake.

Step 9 – Preparing the syringe for administration

• Turn the vial, adapter, and syringe completely upside up (with the syringe on top). Disconnect the filled syringe from the adapter by holding the adapter with one hand and gently turning the syringe counterclockwise.
• Place the vial and attached adapter into the provided sharps container.
• Do not touch the needle tip or allow it to contact any surface. Place the syringe on the clean, flat surface.
• Proceed to Step 10 to inject caplacizumab under the skin of the abdomen. Instructions for healthcare professionals on how to inject Cablivi into a vein are located at the end of this leaflet.

Step 10 – Needle insertion

• Remove the needle by breaking the paper seal of the needle pack and removing the needle with its protective cap.

• Without removing the needle cap, attach the needle to the syringe by turning it clockwise until resistance is felt.
• Pull back the needle safety shield.
• Check the syringe contents. Do not use the medicine if it appears cloudy, contains clumps, or anything else that seems abnormal. Contact your doctor or nursing staff if this occurs.

Step 11 – Preparing the injection site for subcutaneous injection

• Select an appropriate site (“injection site”) on your abdomen for the subcutaneous injection.
• Avoid the area around the navel. Choose a different injection site from the one used the previous day to allow the skin to recover after injection.
• Use the second alcohol wipe to clean the selected injection site.

Step 12 – Administration

• Carefully remove and discard the protective needle cap. Ensure the needle does not touch anything before injection.
• Hold the syringe at eye level with the needle pointing upward.
• Remove air bubbles by gently tapping the side of the syringe so bubbles rise to the top. Then slowly push the plunger until a small amount of liquid appears at the needle tip.
• Gently pinch the cleaned skin between your thumb and index finger to create a skin fold.

• Maintain this skin fold throughout the injection.
• Insert the entire needle into the skin fold at the angle shown in the illustration.
• Push the plunger down completely.

• Withdraw the needle at the same angle as insertion. Do not rub the injection site.

Step 13 – After administration

• Immediately after the injection, place the needle safety shield over the needle until it clicks into place.

• Place the syringe with the needle into a sharps container.

If you use more Cablivi than you should

Overdose is unlikely because one vial contains only a single dose. Inform your doctor if you think you have had an overdose.

If you forget to use Cablivi

If you miss a dose, you should administer it if less than 12 hours have passed since the scheduled time. If more than 12 hours have passed since the dose was due, do not administer the missed dose, but inject the next dose at the usual time.

If you stop using Cablivi

To get the maximum benefit from your treatment, it is important to use Cablivi as prescribed and for the duration your doctor has instructed. Inform your doctor before stopping treatment, as stopping too early may cause your disease to return.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Contact your doctor immediately if any of the following serious adverse effects occur.

Prolonged or excessive bleeding.

Your doctor may decide to monitor you more closely or change your treatment.

Adverse effects reported in a clinical study occurred with the following frequencies:

Very common: may affect more than 1 in 10 people

• bleeding gums
• fever
• fatigue
• headache
• nosebleeds
• rash

Common: may affect up to 1 in 10 people

• eye bleeding
• vomiting blood
• blood in the stool
• black, tarry stools
• stomach bleeding
• bleeding hemorrhoids
• rectal bleeding
• injection site reactions: rash, itching, and bleeding
• brain bleeding shown by sudden severe headaches, vomiting, decreased level of consciousness, fever, sometimes seizures and neck stiffness or neck pain
• muscle pain
• stroke
• blood in the urine
• excessive bleeding during periods
• vaginal bleeding
• coughing up blood
• shortness of breath
• bruising

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cablivi

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

Do not use this medicine after the expiry date stated on the label and packaging after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep in the original container to protect from light.

Cablivi may be stored at a temperature not exceeding 25 °C for a single period of up to 2 months, but not beyond the expiry date. Once removed from refrigeration, Cablivi must not be returned to refrigerated storage. Never expose to temperatures above 30 °C.

Do not use Cablivi if particles or discoloration are observed prior to administration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Contents of Cablivi

• Vial powder

• The active substance is caplacizumab.

Each vial contains 10 mg of caplacizumab.

• The other components are sucrose, anhydrous citric acid, trisodium citrate dihydrate (see section 2 “Cablivi contains sodium”), and polysorbate 80.

• Pre-filled syringe

The pre-filled syringe contains 1 ml of water for injections.

Appearance of Cablivi and contents of the pack

Cablivi is supplied as:

• a white powder for injectable solution in a glass vial, and
• water for injections in a pre-filled syringe for reconstituting the powder.

After dissolving the powder in the solvent, the solution is clear, colourless or slightly yellowish.

Cablivi is available in:

• single packs containing 1 vial of caplacizumab powder, 1 solvent pre-filled syringe, 1 vial adapter, 1 needle, and 2 alcohol wipes
• multiple packs containing 7 single packs
• multi-dose packs containing 7 vials of caplacizumab powder, 7 solvent pre-filled syringes, 7 vial adapters, 7 needles, and 14 alcohol wipes.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Ablynx NV

Technologiepark 21

9052 Zwijnaarde

Belgium

Manufacturer

Ablynx NV

Technologiepark 21

9052 Zwijnaarde

Belgium

Sanofi B.V.

Paasheuvelweg 25

1105 BP Amsterdam

The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

Belgium/Belgium/Belgium Sanofi Belgium Tel/Tel: +32 (0)2 710 54 00	Lithuania Swixx Biopharma UAB Tel: +370 5 236 91 40
Swixx Biopharma EOOD Tel.: +359 (0)2 4942 480	Luxembourg/Luxembourg Sanofi Belgium Tél/Tel: +32 (0)2 710 54 00 (Belgium/Belgium)
Czech Republic Sanofi s.r.o. Tel: +420 233 086 111	Hungary SANOFI-AVENTIS Zrt. Tel.: +36 1 505 0050
Denmark Sanofi A/S Tlf: +45 45 16 70 00	Malta Sanofi S.r.l. Tel: +39 02 39394275
Germany Sanofi-Aventis Deutschland GmbH Tel.: 0800 04 36 996 Tel. from abroad: +49 69 305 70 13	Netherlands Sanofi B.V. Tel: +31 20 245 4000
Estonia Swixx Biopharma OÜ Tel: +372 640 10 30	Norway sanofi-aventis Norge AS Tlf: +47 67 10 71 00
Greece sanofi-aventis Μονοπρόσωπη AEBE Tel: +30 210 900 16 00	Austria sanofi-aventis GmbH Tel: +43 1 80 185 – 0
Spain sanofi-aventis, S.A. Tel: +34 93 485 94 00	Poland Sanofi Sp. z o.o. Tel.: +48 22 280 00 00
France Sanofi Winthrop Industrie Tél: 0 800 222 555 Call from abroad: +33 1 57 63 23 23	Portugal Sanofi - Produtos Farmacêuticos, Lda. Tel: +351 21 35 89 400
Croatia 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	Slovenia Swixx Biopharma d.o.o. Tel: +386 1 235 51 00
Iceland Vistor hf. Sími: +354 535 7000	Slovakia Swixx Biopharma s.r.o. Tel: +421 2 208 33 600
Italy Sanofi S.r.l. Tel: 800 536389	Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300
Cyprus C.A. Papaellinas Ltd. Tel: +357 22 741741	Sweden Sanofi AB Tel: +46 (0)8 634 50 00
Latvia 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

Date of the most recent review of this leaflet:

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

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This information is intended for healthcare professionals only:

The intravenous bolus injection of Cablivi administered at the beginning of treatment must be given by a healthcare professional. Preparation of a dose of Cablivi for intravenous injection must be performed in the same way as for a subcutaneous injection (see the Instructions for use, steps 1 to 9, in section 3).

Cablivi may be administered intravenously by connecting the prepared syringe to standard Luer lock connectors of intravenous lines or by using an appropriate needle. The line may be flushed with sodium chloride 9 mg/ml (0.9%) solution for injection.