Cevenfacta 2 mg (90 KIU) powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

CEVENFACTA 1 mg (45 kIU), powder and solvent for injectable solution

CEVENFACTA 2 mg (90 kIU), powder and solvent for injectable solution

CEVENFACTA 5 mg (225 kIU), powder and solvent for injectable solution

eptacog beta (activated)

This medicinal product is subject to additional monitoring, which will allow quicker detection of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

Read this entire leaflet carefully before you start using this medicine, as 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, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, since it may harm them.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What CEVENFACTA is and what it is used for

CEVENFACTA contains the active substance eptacog beta (activated), a recombinant human coagulation factor VIIa (rFVIIa).

CEVENFACTA is used in adults and adolescents (12 years of age or older) who were born with haemophilia A or B and who have developed inhibitors (antibodies). It is used for:

• treatment of bleeding episodes,
• management of bleeding during surgery.

How CEVENFACTA works

This medicine works by forming a blood clot at the site of bleeding when the body's own clotting factors do not function properly.

2. What you need to know before using CEVENFACTA

Do not use CEVENFACTA

• if you are allergic to eptacog beta (activated) or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to rabbits or rabbit proteins.

Warnings and precautions

Before starting your treatment with CEVENFACTA, inform your doctor:

• If you have a history of atherosclerosis (narrowing of arteries due to disease), coronary artery disease (heart disease due to narrowing of blood vessels supplying the heart), cerebrovascular disease (disease of blood vessels supplying the brain), crush injury, sepsis (serious blood infection), or blood clots.
• If you have heart disease, heart failure, or an abnormal heart rhythm.
• If you have ever had a pulmonary clot (in the lungs) or undergone heart surgery.
• If you currently have or have previously had any other medical condition.

Patients with a known allergy to casein may have an increased risk of hypersensitivity reactions. If signs or symptoms of hypersensitivity occur, treatment must be discontinued immediately and you should contact your doctor without delay. Symptoms may include hives (swelling with itching under the skin), itching, rash, difficulty breathing, swelling around the mouth and throat, chest tightness, wheezing, dizziness or fainting, and decreased blood pressure.

Although not observed, the following reactions may occur with treatment using CEVENFACTA:

• Blood clots in the arteries of the heart (which may cause heart attack or angina), in the brain (which may cause stroke), or in the lungs or deep veins. Symptoms may include sweating and pain in the arms, legs, or abdomen, chest pain, difficulty breathing, loss of sensation or movement, and altered consciousness or speech.
• Hypersensitivity or anaphylactic reactions. Symptoms may include hives (swelling with itching under the skin), itching, rash, difficulty breathing, swelling around the mouth and throat, chest tightness, wheezing, dizziness or fainting, and decreased blood pressure.
• Inhibitors (antibodies) that may cause bleeding problems.

If you experience any of these reactions, consult your doctor before continuing to use CEVENFACTA.

It is important to record the batch number of your CEVENFACTA. Each time you use a new CEVENFACTA container, write down the date and the batch number (shown on the container after "Lot") and keep this information in a safe place.

Adolescents

The warnings and precautions mentioned apply to both adults and adolescents (12 years of age or older).

Other medicines and CEVENFACTA

Inform your doctor if you have recently taken or may need to take any other medicines.

You should consult your doctor before using CEVENFACTA if

• you are taking or have recently taken another activated factor VII, activated or non-activated prothrombin complex concentrates,
• you are taking or have recently taken factor XIII,

as combining these medicines with CEVENFACTA may increase the risk of thromboembolic events (formation of blood clots in veins).

You should consult your doctor before starting treatment with CEVENFACTA in combination with these medicines.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

Driving and use of machines

Dizziness may occur after administration of CEVENFACTA. You should avoid driving or operating machinery while experiencing this symptom.

CEVENFACTA contains sodium

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

3. How to use CEVENFACTA

The use of this medicine should be initiated and supervised by a physician experienced in the treatment of hemophilia and/or bleeding disorders.

CEVENFACTA comes as a powder and must be prepared (reconstituted) with solvent and injected into a vein (intravenous injection). Refer to the instructions in the user guide located at the end of this leaflet (section 7).

Self-administration

Drug injection requires special training. Do not attempt self-administration unless your doctor or your hemophilia treatment center has trained you to do so.

Many people with inhibitors learn to self-inject, either alone or with the help of a family member. Once trained, you will need additional injection equipment, separate from your CEVENFACTA kit, to properly treat your bleeding episodes at home. Make sure you have all the necessary injection equipment before preparing the medicine for injection. This additional injection equipment will be provided by your healthcare professional (e.g., your pharmacist or your hemophilia treatment center).

CEVENFACTA may be administered at a hemophilia treatment center, your doctor's office, or at home. It is important to start treatment at the first sign of bleeding to control it effectively.

Begin treatment for bleeding as soon as possible, ideally within 2 hours.

? For mild or moderate bleeding (e.g., joint, superficial muscle, soft tissue, or mucous membranes), treat yourself as soon as possible, ideally at home.

? For severe bleeding (e.g., limb [arm or leg] hemorrhage or life-threatening bleeding, intracranial [in the skull] or gastrointestinal [in the stomach or intestine] hemorrhage), contact your doctor immediately.

Severe bleeding is generally treated in a hospital, but the first dose of CEVENFACTA may be administered while en route to the medical facility.

Do not self-treat for more than 24 hours without consulting your doctor.

? Each time you use this medicine, inform your healthcare professional as soon as possible.

? If bleeding is not controlled within 24 hours, contact your healthcare professional or emergency services immediately. Hospital care is usually required.

For reconstitution of the medicine before administration, follow the instructions in the Instructions for Use located at the end of this leaflet (section 7).

Inject the solution into the vein within 2 minutes or less.

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

Dosage

Your healthcare provider will determine how much CEVENFACTA to use and when to administer it, based on your weight, condition, and the type of bleeding.

Treatment of bleeding episodes

Treatment with this medicine should begin as soon as a bleeding episode occurs.

Mild and moderate bleeding:

Home treatment should not last longer than 24 hours for mild to moderate bleeding episodes. Continuing home treatment beyond 24 hours should only be considered after consultation at a hemophilia treatment center.

Severe bleeding:

Seek immediate medical attention if signs or symptoms of severe bleeding occur at home.

To avoid any delay in treatment, the first dose may be administered while on the way to the hemophilia treatment center or doctor's office.

Follow exactly the administration instructions provided in this leaflet or as directed by your doctor. If in doubt, consult your doctor again.

Method of administration

For reconstitution of the medicine before administration and administration instructions, follow the guide in the Instructions for Use located at the end of this leaflet (section 7).

If you use more CEVENFACTA than you should

If you use too much CEVENFACTA, go to the doctor immediately.

If you forget to use CEVENFACTA:

If you forget to use CEVENFACTA, consult your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody experiences them.

Frequent adverse effects

(may affect up to 1 in 10 people)

• Dizziness
• Headache
• Discomfort at the injection site
• Bruising at the injection site (haematoma)
• Increased body temperature
• Postoperative haematoma
• Injection-related reaction

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, 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 CEVENFACTA

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 on the carton after EXP. The expiry date refers to the last day of the month indicated.

Store below 30 °C.

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

To reconstitute CEVENFACTA, use only the materials supplied in the kit.

After reconstitution, the product should be stored in the vial and administered within 4 hours. Any unused solution must be discarded 4 hours after reconstitution.

Do not use this medicine if you notice that the liquid contains particles or appears cloudy after mixing.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

Composition of CEVENFACTA

• The active substance is recombinant coagulation factor VIIa (eptacog beta (activated)).
• The other excipients are:

Powder: arginine hydrochloride, isoleucine, sodium citrate dihydrate, glycine, lysine hydrochloride, polysorbate 80, hydrochloric acid (for pH adjustment).

Solvent: water for injections.

See section 2, "CEVENFACTA contains sodium".

The powder for injectable solution contains: 1 mg/vial (corresponding to 45 kIU/vial), 2 mg/vial (corresponding to 90 kIU/vial), 5 mg/vial (corresponding to 225 kIU/vial).

After reconstitution, the concentration of the solution is approximately 1 mg/ml (45 kIU/ml) of eptacog beta (activated). 1 kIU equals 1,000 IU (International Units).

Appearance of CEVENFACTA and contents of the pack

The vial of powder contains a white to off-white lyophilized powder, and the pre-filled syringe of solvent contains a clear, colourless solution. The reconstituted solution should be clear to slightly opalescent.

Each CEVENFACTA pack contains:

• 1 glass vial with powder for an injectable solution,
• 1 sterile vial adapter for reconstitution, equipped with a 5 µm filter,
• 1 pre-filled syringe with water for injections,
• 1 plunger rod with a rear stopper.

Presentations: 1 mg (45 kIU), 2 mg (90 kIU) and 5 mg (225 kIU).

Marketing Authorisation Holder

Laboratoire français du Fractionnement et des Biotechnologies

Tour W

102 Terrasse Boieldieu, 19th Floor

92800 Puteaux

France

Manufacturer

LFB Biotechnologies

Zone d’activité de Courtabœuf

3 Avenue des Tropiques

91940 Les Ulis

France

+33 1 69 82 70 10

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

Date of the most recent revision of this leaflet:

Other sources of information

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

This leaflet is available on the European Medicines Agency website in all languages of the European Union/European Economic Area.

INSTRUCTIONS FOR USE

READ THESE INSTRUCTIONS CAREFULLY BEFORE BEGINNING TO USE CEVENFACTA

CEVENFACTA is supplied as a powder. Before injection, it must be prepared (reconstituted) with the solvent provided in the syringe. The solvent is water for injections. The reconstituted CEVENFACTA must be injected into a vein (intravenous use only).

This kit provides the necessary equipment for reconstituting the medicine. Additional materials are required to inject the medicine after reconstitution. These materials will be supplied by your healthcare professional (e.g., your pharmacist or your haemophilia treatment centre).

Your doctor or nurse will show you and/or your caregiver how to prepare and inject CEVENFACTA. Do not use this kit without proper training from your healthcare professional or your haemophilia treatment centre.

Use a clean, germ-free (aseptic) technique when preparing and injecting the medicine.

A CEVENFACTA kit contains:

• 1 glass vial with powder for an injectable solution
• 1 sterile vial adapter for reconstitution, equipped with a 5 µm filter
• 1 pre-filled syringe with water for injections
• 1 plunger rod with a rear stopper

You will also need a sterile injection set (cannula and butterfly needle), a sterile plastic syringe, sterile alcohol-impregnated swabs, and a sharps disposal container compliant with local regulations and applicable laws. These materials are not included in the CEVENFACTA pack. These materials will be supplied by your healthcare professional (e.g., your pharmacist or your haemophilia treatment centre).

1. Gather equipment and prepare the vial

• Take out the number of CEVENFACTA kits required to administer the prescribed dose, a sterile injection set (not supplied), and an alcohol-impregnated swab (not supplied).

Do not use the kit if the tamper-evident seal is broken or if there are signs that the kit is contaminated. Use a new one instead.

• Check the expiry date on the side of the kit (Fig. A).

Do not use after the expiry date.

• Check the name, concentration, and colour of the box to ensure it contains the correct product (the 1 mg pack is yellow, the 2 mg is green, and the 5 mg is purple).

• Work on a clean, flat surface before starting the reconstitution steps for CEVENFACTA.

• Wash your hands with soap and water and dry them with a clean towel or air dry (Fig. B).

• Remove the contents of one kit and an alcohol swab. Place everything on a clean surface (Fig. C).

• Inspect all components in the kit. Ensure each vial has a syringe of matching colour.

Do not use the contents if they have been dropped or are damaged. Use a new kit instead.

• Allow the vial and pre-filled syringe to reach room temperature if necessary. Hold them until they feel as warm as your hands.

Do not use the vial or pre-filled syringe heated in any other way.

• Remove the plastic cap from the vial (Fig. D).

If the plastic cap is loose or the vial comes without a cap, do not use it.

• Clean the rubber stopper with an alcohol-impregnated swab (Fig. E) and allow it to air dry for a few seconds to ensure it is as germ-free as possible.

• After cleaning, avoid touching the rubber stopper with your fingers and do not let it come into contact with any other object before placing the vial adapter, as this could contribute to germ transmission.

1. Attach the vial adapter

• Peel off the paper protective cover from the vial adapter packaging (Fig. F).

If the protective paper is not fully sealed or is torn, do not use the adapter.

Do not remove the vial adapter from its protective packaging with your fingers. If you touch the spike of the adapter with your fingers, you may transmit germs.

• Place the vial on a clean, flat surface and hold it with one hand. With the other, place the plastic cover (with the vial adapter inside) directly onto the vial and insert the spike of the adapter into the centre of the grey rubber stopper.

• Press down firmly so that the spike of the adapter pierces the rubber stopper (you may hear and/or see it click into place) (Fig. G).

• Remove the plastic packaging of the adapter by gently pressing and lifting it upwards (Fig. H).

Once the plastic cover has been removed, do not touch the top of the adapter to avoid germ transmission.

NOTE: The 5 mg vial adapter may not sit flat against the vial, but it is still fully functional. As mentioned above, your CEVENFACTA kit contains only one vial adapter (the one appropriate for the vial included in the kit).

1. Attach the pre-filled syringe and insert the plunger rod

• Remove the syringe cap by holding the syringe body with one hand and using the other to unscrew it (turning to the left) (Fig. I).

Avoid touching the syringe tip to prevent transferring germs from your fingers.

If the syringe cap is loose or the syringe came without one, do not use it.

• Hold the edges of the vial adapter and screw the pre-filled syringe onto it by turning it several times to the right until resistance is felt (Fig. J).

Be careful not to overtighten, as you will need to remove the syringe later.

• To insert the plunger rod into the syringe, hold the upper end of the plunger rod with one hand and the syringe body with the other.

• Insert the plunger rod into the syringe and then screw it in with a few turns (turning to the right) so it is securely attached to the grey rubber piston of the syringe (Fig. K).

1. Mix the medicine in the vial

• Very slowly push the plunger rod all the way down to inject all the liquid from the syringe into the vial (Fig. L).

Do not push too quickly, as excessive foam and air may form in the vial.

• Gently swirl the vial or carefully roll it between your hands to dissolve all the powder (Fig. M).

Do not shake the vial, as this may cause foam and air formation.

• Visually inspect the final solution (Fig. N) to ensure it is clear or slightly opalescent. All powder should be dissolved, and no particles should remain floating in the liquid.

Do not use the product if the solution contains any particles or appears cloudy after mixing. Repeat the process with a new kit.

1. Remove the empty syringe from the vial adapter

• Without reintroducing any medicine into the syringe, unscrew it from the vial adapter (turning to the left) until completely removed (Fig. O).

• Dispose of the empty syringe in an authorised sharps container (Fig. P).

Do not remove the adapter from the vial.

Do not touch the top end of the Luer-Lock adapter. If you do, you may transmit germs from your fingers.

1. Mix additional vial(s) and inject the dose

• If your dose requires more than one vial, repeat the previous steps with additional kits until the required dose is obtained.

• Withdraw the liquid medicine from the vial(s) using a sterile syringe provided by your pharmacy, large enough to hold the prescribed dose.

• CEVENFACTA must be administered within 4 hours after reconstitution (Fig. Q).

Do not use if more than 4 hours have passed since reconstitution.

• CEVENFACTA may be administered by intravenous injection over 2 minutes or less into a vein, as directed by your healthcare professional.

1. Dispose of empty medicine vials

• After reconstitution and injection, safely dispose of the vial with its adapter, the injection syringe, and any other disposable materials in an authorised sharps container (Fig. R).

Do not throw in household waste.

Do not separate the vial from the vial adapter before disposal.

Do not reuse any of the components in the kit.

Follow local regulations and guidelines for proper disposal of the sharps container.

Storage

CEVENFACTA is supplied in a kit that must be stored below 30 °C.

Do not open the kit components until ready for use.

Do not freeze or store reconstituted CEVENFACTA solution in syringes.

Avoid exposing the reconstituted CEVENFACTA solution to direct light.

Important information

CEVENFACTA is for intravenous injection only (into a vein). Do not inject by any other route, such as under the skin (subcutaneous) or into a muscle (intramuscular). Contact your doctor, nurse, or pharmacist if you have any problems.