Prospect: 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 medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, even if they do not appear in this prospect. See section 4.

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

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

- the treatment of bleeding episodes,

- the management of bleeding during surgery.

How CEVENFACTA works

This medication acts by forming a blood clot at the site of bleeding, when the body's own coagulation factors do not function.

Do not use CEVENFACTA

- if you are allergic to eptacog beta (activated) or any of the other components of this medication (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 (when arteries narrow due to disease), coronary artery disease (heart disease due to narrowing of blood vessels that irrigate the heart), cerebrovascular disease (disease of blood vessels that irrigate the brain), crushing injury, septicemia (severe blood infection) or blood clots.
• If you have heart disease, heart failure or an abnormal heart rhythm.
• If you have ever had a pulmonary embolism (pulmonary) or have undergone cardiac surgery.
• If you have or have had any other medical condition.

Patients with known casein allergy may have a higher risk of hypersensitivity reactions. If signs or symptoms of hypersensitivity appear, discontinue treatment and seek immediate medical attention. Symptoms may include urticaria (skin swelling with pruritus), itching, hives, difficulty breathing, swelling around the mouth and throat, chest oppression, wheezing, dizziness or fainting, and decreased blood pressure.

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

• Blood clots in the heart arteries (which may cause a heart attack or angina) or in the brain (which may cause a stroke) or in the lungs or deep veins. Symptoms may include sweating and pain in the arms, legs or abdomen, chest pain, difficulty breathing, numbness or loss of movement, and alteration of consciousness or speech.
• Hypersensitivity or anaphylactic reactions. Symptoms may include urticaria (skin swelling with pruritus), itching, hives, difficulty breathing, swelling around the mouth and throat, chest oppression, 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 essential to record the batch number of your CEVENFACTA. Each time you use a new CEVENFACTA container, note the date and batch number (listed on the container, after «Lot») and store that information in a safe place.

Adolescents

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

Other medications and CEVENFACTA

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

You must consult your doctor before using CEVENFACTA if

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

since the combination of these medications with CEVENFACTA may increase the risk of thromboembolic events (blood clots in veins).

You must consult your doctor before starting to use CEVENFACTA with these medications.

Pregnancy, breastfeeding and fertility

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

Driving and operating machinery

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

CEVENFACTA contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per injection, that is essentially «sodium-free».

The use of this medication should be initiated and supervised by a doctor with experience in the treatment of hemophilia and/or bleeding disorders.

CEVENFACTA comes in powder form and must be prepared (reconstituted) with a solvent and injected into a vein (intravenous injection). Consult the usage guide instructions found at the end of this prospectus (section 7).

Self-administration

Medication injection requires special training. Do not attempt self-administration unless your doctor or hemophilia treatment center has taught you how to do it.

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

CEVENFACTA can be injected at a hemophilia treatment center, at your doctor's office, or at home. It is essential to treat the first sign of bleeding to control it.

Start the bleeding treatment as soon as possible, ideally within 2 hours.

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

?In the case of severe bleeding (e.g., limb hemorrhage or life-threatening, intracranial hemorrhage or gastrointestinal hemorrhage), contact your doctor.

Generally, severe bleeding is treated in the hospital, but the first dose of CEVENFACTA can be administered on the way to the healthcare facility.

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

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

?If bleeding is not controlled within 24 hours, contact your healthcare professional or emergency services immediately. Generally, you will need hospital assistance.

To reconstitute the medication before administration, follow the guidelines in theUsage Instructionsfound at the end of this prospectus (section 7).

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

Follow exactly the administration instructions for this medication indicated by your doctor. In case of doubt, consult your doctor again.

Dose

Your healthcare professional will indicate the amount of CEVENFACTA to use and when to administer the medication based on your weight, condition, and type of bleeding.

Bleeding episode treatment

The treatment with this medication should be started as soon as the bleeding episode occurs.

Mild and moderate bleeding:

Home treatment should not last more than 24 hours in the case of mild to moderate bleeding episodes. Continuing home treatment after 24 hours should only be considered after a consultation at a hemophilia treatment center.

Severe bleeding:

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

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

Follow exactly the administration instructions for the medication contained in this prospectus or indicated by your doctor. In case of doubt, consult your doctor again.

Administration form

To reconstitute the medication before administration and administration instructions, follow the guidelines in theUsage Instructionsfound at the end of this prospectus (section 7).

If you use more CEVENFACTA than you should

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

If you forgot to use CEVENFACTA:

If you forgot to use CEVENFACTA, consult your doctor.

If you have any other questions about using this medication, ask your doctor.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Frequent Adverse Effects

(may affect up to 1 in 10 people)

• Dizziness
• Headache
• Discomfort at the injection site
• Cardinal signs at the injection site (hematoma)
• Increased body temperature
• Postoperative hematoma
• Injection-related reaction

Reporting 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 prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Do not use this medication after the expiration date that appears on the label and on the box after EXP. The expiration date is the last day of the month indicated.

Store below 30 °C.

Do not freeze.

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

To reconstitute CEVENFACTA, use exclusively the material provided in the kit.

After reconstitution, the product must be stored in the vial and administered within a period of 4 hours. Any remaining solution must be discarded 4 hours after reconstitution.

Do not use this medication if you observe that the liquid contains particles or is cloudy after mixing.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of medications that you no longer need. In this way, you will help protect the environment.

Composition of CEVENFACTA

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

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

Solvent:water for injection preparations.

See section 2 «CEVENFACTA contains sodium»

The powder for injectable solution contains: 1 mg/vial (which corresponds to 45 kIU/vial), 2 mg/vial (which corresponds to 90 kIU/vial), 5 mg/vial (which corresponds 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 is equal to 1,000 IU (International Units).

Appearance of CEVENFACTA and contents of the package

The vial of powder contains lyophilized powder of white to off-white and the pre-loaded syringe contains a transparent and colorless solution. The reconstituted solution must be transparent to slightly opaque.

Each package of CEVENFACTA contains:

• 1 glass vial with powder for injectable solution,
• 1 sterile vial adapter for reconstitution, equipped with a 5 µm filter,
• 1 syringe pre-loaded with water for injections,
• 1 stopper with backstop.

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

Marketing Authorization Holder

Laboratoire français du Fractionnement et des Biotechnologies

Tour W

102 Terrasse Boieldieu, 19ème Étage

92800 Puteaux

France

Manufacturer

LFB Biotechnologies

Zone d’activité de Courtab?uf

3 Avenue des Tropiques

91940 Les Ulis

France

+33 1 69 82 70 10

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

Last update of this leaflet:

Other sources of information

The 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 in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

INSTRUCTIONS FOR USE

READ THIS LEAFLET CAREFULLY BEFORE STARTING TO USE CEVENFACTA

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

This kit provides the necessary equipment to reconstitute the medication. Additional materials are needed to inject the medication after reconstitution. These materials will be provided by your healthcare professional (e.g., your pharmacist or your hemophilia treatment center).

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 hemophilia treatment center.

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

This CEVENFACTA kit contains:

• 1 glass vial with powder for injectable solution
• 1 sterile vial adapter for reconstitution, equipped with a 5 µm filter
• 1 syringe pre-loaded with water for injection preparations
• 1 stopper with backstop

You will also need a sterile injection set (needle and butterfly), a plastic syringe, alcohol-impregnated sterile gauze, and a puncture-proof container that meets local regulations and guidelines.These materials are not included in the CEVENFACTA package.These materials will be provided by your healthcare professional (e.g., your pharmacist or your hemophilia treatment center).

1) Gather the equipment and prepare the vial

• Remove the number of CEVENFACTA kits needed to administer the prescribed dose, a sterile injection set (not provided), and an alcohol-impregnated gauze (not provided).

Do not use the kit if the safety seal is broken or if there are signs of contamination.Use a new one instead.

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

Do not use it after the expiration date.

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

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

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

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

• Inspect all the elements contained in the kit. Make sure each vial has a syringe of the same color.

Do not use the contents if it has fallen or is damaged.Use a new kit instead.

• Let the vial and syringe pre-loaded reach room temperature if necessary. To do this, hold them until you feel them as warm as your hands.

Do not use the vial and syringe pre-loaded 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 gauze(Fig. E)and let it dry in the air 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 objectbefore placing the vial adapter, as this could contribute to the transmission of germs.

2) Place the vial adapter

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

If the paper protector is not completely sealed or is broken, 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 and flat surface and hold it with one hand. With the other hand, place the plastic cover (with the vial adapter inside) directly on the vial and insert the spike of the adapter into the gray rubber stopper.

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

• Remove the plastic cover from the adapter by pressing lightly and lifting it upwards(Fig. H).

Once you have removed the plastic cover, do not touch the top of the adapter to avoid transmitting germs.

NOTE:The 5 mg vial adapter may not be flat in contact with the vial, but it is still fully functional. As mentioned earlier, your CEVENFACTA kit contains a single vial adapter (the one suitable for the vial included in the kit).

3) Place the pre-loaded syringe and introduce the plunger rod

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

Avoid touching the needle tip to prevent transmitting germs from your fingers.

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

• Hold the syringe adapter and screw the syringe pre-loaded onto it by turning it to the right a few times until you feel resistance(Fig. J).

Be careful not to tighten it too much, as you will need to remove the syringe later.

• To place the plunger rod in the syringe, hold the top 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 a few turns (turning to the right) to secure it to the piston of the syringe(Fig. K).

4) Mix the medication in the vial

• Push the plunger rod slowly to the bottom of the syringe to inject all the liquid from the syringe into the vial(Fig. L).

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

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

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

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

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

5) Remove the empty syringe from the vial adapter

• Without re-introducing any medication into the syringe, unscrew it from the vial adapter (turning to the left) until it is completely removed(Fig. O).

• Dispose of the empty syringe in a puncture-proof container(Fig. P).

Do not remove the vial adapter.

Do not touch the top of the vial adapter with the Luer-Lock stopper. If you touch it, you may transmit germs from your fingers.

6) Mix the vial (or vials) extra(s) and inject the dose

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

• Extract the liquid medication from the vial (or vials) using a sterile syringe provided by your pharmacy that is large enough to contain the prescribed dose.

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

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

• CEVENFACTA can be used by intravenous injection of 2 minutes or less in the vein, as indicated by your healthcare professional.

7) Dispose of the empty medication vials

• After reconstitution and injection, dispose of the vial with its adapter, the injection syringe, and any other disposable materials in a puncture-proof container(Fig. R).

Do not dispose of household waste.

Do not separate the vial from the vial adapter before disposing of them.

Do not re-use any of the elements contained in the kit.

Follow local regulations and guidelines for the proper disposal of the puncture-proof container.

Storage

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

Do not open the contents of the kit until you are ready to use them.

Do not freeze or store in syringes containing the reconstituted CEVENFACTA solution.

Avoid exposing the reconstituted CEVENFACTA solution to direct light.

Important information

CEVENFACTA is only injected into a vein (intravenous administration). Do not inject it 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.