PATIENT INFORMATION LEAFLET

FibCLOT 1.5g

Powder and solvent for injectable solution and for infusion

human fibrinogen

Read this 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, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1. What is FibCLOT and what it is used for

2. What you need to know before you start using FibCLOT

3. How to use FibCLOT

4. Possible side effects

5. Storage of FibCLOT

6. Contents of the pack and additional information

What is FibCLOT

It is a medication that belongs to the group of antihemorrhagics. The active ingredient is human fibrinogen, a protein naturally present in the body. The function of this protein is to ensure that the blood clots normally and prevent excessive bleeding.

What is FibCLOT used for

It is usedin all age groupsto compensate for the lack of human fibrinogen and, in this way, treat bleeding (hemorrhages) in patients with congenital fibrinogen deficiency.

Congenital fibrinogen deficiency is a hereditary disease characterized by a lower than normal or absence of a protein called fibrinogen. This deficiency can cause prolonged bleeding.

No use FibCLOT

If you are allergic to the active ingredient (human fibrinogen) or to any of the other components of this medication (listed in section 6. "Contents of the package and additional information").

Inform your doctor if you are allergic to any medication.

Warnings and precautions:

Consult your doctor, pharmacist, or nurse before starting to use FibCLOT.

Traceability

To improve the traceability of biological medicines, the name and batch number of the administered medication must be clearly recorded.

Blood clot risk

With high doses or repeated administrations, this medication may increase the risk of blood clots in the blood vessels.

Therefore, your doctor must weigh the benefits of this medication against the risk of blood clots, especially:

• If you have had a heart attack (history of coronary heart disease or myocardial infarction).
• If you have liver disease.
• If you have recently undergone surgery.
• If you are about to undergo surgery.
• In newborns (neonates).
• If you are more likely than normal to suffer from blood clots.

Your doctor may request additional tests to monitor this risk.

Allergic risk

Your doctor will inform you of the warning signs of an allergic reaction or a severe allergic reaction (anaphylactic reaction) (see section 4. "Possible side effects"). If any of these effects appear, you must stop using this medication immediately.

Viral safety

This medication is made from human plasma (the liquid part of the blood).

When biological medicines or human plasma are prepared, certain measures are taken to prevent the transmission of infections to patients. Some of these measures are:

• Careful selection of blood and plasma donors to ensure that those with a risk of being carriers of infections are excluded.
• Checking each donation and plasma mix for signs of viral infections.
• Including stages in the processing of blood or plasma that can inactivate or eliminate viruses.

Despite these measures, when biological medicines or human plasma-derived products are administered, the risk of transmission of an infection cannot be completely ruled out. This also applies to unknown or emerging viruses and other types of infections.

The measures taken are considered effective for encapsulated viruses, such as the human immunodeficiency virus (HIV or AIDS virus), hepatitis B virus, and hepatitis C virus, and for non-encapsulated hepatitis A virus.

The measures taken may have limited effectiveness against non-encapsulated viruses such as parvovirus B19. Parvovirus B19 infection can be severe in pregnant women (fetal infection) and in people with weakened immune systems or certain types of anemia (e.g., sickle cell disease or hemolytic anemia).

If you receive human plasma-derived products regularly, your doctor may recommend that you consider vaccination against hepatitis A and B.

Immune risk

In the context of other congenital deficiencies, therapy with coagulation factors has been associated with immune reactions, but no data are available for fibrinogen.

Children and adolescents

The warnings and precautions mentioned above are also applicable to children and adolescents.

Use of FibCLOT with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those obtained without a prescription.

No interactions have been observed between this treatment and other medications to date. However, it should not be mixed with other products and/or medications.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication. This medication should only be used during pregnancy and breastfeeding on the recommendation of your doctor.
• Consult your doctor if you discover that you are pregnant during treatment, as only your doctor can determine if you need to continue with it.

Driving and operating machinery

The influence of this medication on the ability to drive and operate machinery is negligible.

FibCLOT contains sodium.

This medication contains up to 3 mmol (or 69 mg) of sodium (the main component of table salt) per vial. This amount is equivalent to 3.45% of the maximum daily recommended sodium intake for an adult.

If you are following a low-sodium diet, you should take this into account.

Treatment should begin under the supervision of a doctor with experience in treating congenital fibrinogen deficiency.

Dose

Your doctor will determine the appropriate dose and frequency, which will depend on the following factors:

• Your body weight,
• The severity of your condition,
• The location and extent of bleeding, or the nature of yoursurgical intervention,
• Your overall health.

Your doctor will recommend that you have blood tests during treatment to check the amount of fibrinogen in your body.

Depending on the test results, your doctor may decide to adjust the dose and frequency of injections.

Administration frequency

Your doctor will determine how often the injections should be administered.

They will also adjust the number of injections based on the severity of bleeding and the effectiveness of treatment.

Information on treatment frequency and duration in various situations can be found in the section reserved for healthcare professionals at the end of this prospectus.

Administration form:

This medication must be injected into a vein. It is mandatory to use a perfusion set with a 15µm filter, such as the one supplied with the packaging.

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

If you use more FibCLOT than you should

To avoid the risk of overdose, your doctor will perform periodic blood tests to check the amount of fibrinogen in your body.

In the event of an overdose, the risk of abnormal blood clot formation cannot be ruled out.

Like all medications, this medication may cause side effects, although not everyone will experience them.

The most serious side effects are:

• Allergic reactions:like with any intravenous protein product, allergic reactions may occur. In some cases, these reactions have worsened to become a severe allergic reaction, sometimes with a pronounced drop in blood pressure (anaphylactic shock).

The warning signs of allergic reactions are:

• burning and tingling sensation at the injection site,
• tingling,
• redness, itching, and rash,
• hives,
• skin inflammation,
• pallor,
• swelling of the face or throat,
• cough,
• whistling (similar to asthma),
• chest tightness,
• rapid heart rate,
• low blood pressure,
• extreme fatigue (lethargy),
• restlessness,
• chills,
• sensation of illness (nausea), vomiting,

• Blood clots:blood clots may form in the circulatory system. These may cause:

• heart attack, whose warning signs are sudden chest pain or difficulty breathing;
• stroke, whose warning signs are sudden muscle weakness, loss of sensation and/or balance, decreased alertness, or difficulty speaking;
• severe disease called pulmonary embolism (blood clot obstructing a lung artery), whose warning signs are chest pain, difficulty breathing, or coughing up blood;
• clot in a vein (deep vein thrombosis), whose warning signs are redness, warmth, pain, tenderness, or swelling in one or both legs.

The following side effects arecommon(may affect up to1 in 10infusions):

• headache.

The following side effects areuncommon(may affect up to1 in 100infusions):

• allergic reaction (such as anaphylactic shock, pallor, vomiting, cough, low blood pressure, chills, urticarial rash; see also the section «Allergic reactions»),
• dizziness,
• vomiting (associated with headache)
• ringing in the ears,
• blood circulation disorders (deep vein thrombosis, superficial phlebitis),
• difficulty breathing (asthma),
• skin rash, redness of the skin, skin irritation, night sweats,
• sensation of heat.

Children and adolescents

The frequency, type, and severity of side effects are similar in pediatric patients (from birth to 17 years inclusive) and adults, except for allergic reactions or anaphylactic reactions, which occurred more frequently in the pediatric population.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on 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 the box. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C. Do not freeze.

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

The product must be used immediately after reconstitution. Do not store the reconstituted product.

Do not use this medication if the reconstituted solution is cloudy or contains sediment.

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

Composition of FibCLOT

The active ingredient is human fibrinogen (1.5 g per vial). After reconstitution with 100 mL of water for injection, FibCLOT contains 15 mg/mL of human fibrinogen.

The other components are arginine hydrochloride, isoleucine, lysine hydrochloride, glycine, sodium citrate dihydrate, and solvent (water for injection).

Appearance of the product and contents of the package

This medicinal product is presented in the form of a powder accompanied by a solvent for solution for injection in glass vials, a transfer set, and a perfusion set with a 15 µm filter.

The reconstituted solution must be practically colorless and slightly opalescent (it must have a pearlescent luster).

Holder of the marketing authorization:

Laboratoire français du Fractionnement et des Biotechnologies

Tour W–102 Boieldieu 19ème Étage, 92800 Puteaux, FRANCE

Phone: +33(0) 1 69 82 70 10

Fax: +33(0) 1 69 82 19 03

Responsible for manufacturing:

LFB BIOMEDICAMENTS

59 rue de Trévise, 59000 Lille, FRANCE

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

LFB BIOTERAPIAS HISPANIA

C/ Diego de León 47

28006 Madrid

(Spain)

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Germany, Austria, Spain, Greece, United Kingdom: FibCLOT

Denmark, Finland, Hungary, Luxembourg, Norway, Netherlands, Sweden: Fibclot

Belgium: Fibclot 1.5 g, powder and solvent for solution for injection/for perfusion

Italy: Fibriclotte

Revision date of this leaflet: 06/2024

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This information is intended solely for healthcare professionals:

The treatment should be initiated under the supervision of a doctor with experience in the treatment of coagulation disorders.

Dosage

The dose and duration of therapy depend on the severity of the disorder, the location and magnitude of the hemorrhage, as well as the patient's clinical status.

The fibrinogen concentration (functional) should be determined in order to calculate the individual dose; in addition, the amount and frequency of administration should be calculated for each patient individually by determining the fibrinogen concentration in plasma and continuous monitoring of the patient's clinical status and other replacement therapies used.

The normal plasma fibrinogen concentration ranges from 1.5 to 4.5 g/L. In congenital hypofibrinogenemia or afibrinogenemia, the critical plasma fibrinogen concentration below which bleeding may occur is approximately between 0.5 and 1.0 g/L.

In the case of major surgery, it is essential to monitor replacement therapy by coagulation tests.

Treatment of bleeding and perioperative prophylaxis in patients with congenital hypofibrinogenemia or afibrinogenemia and known bleeding tendency.

To treat non-surgical hemorrhagic episodes, it is recommended to increase the fibrinogen concentration to 1.0 g/L and maintain this concentration until hemostasis is controlled, and above 0.5 g/L until healing has completed.

To prevent excessive bleeding during surgical procedures, prophylactic treatment is recommended to increase the fibrinogen concentration to 1.0 g/L and maintain this concentration until hemostasis is controlled, and above 0.5 g/L until healing has completed.

In the case of a surgical procedure or the treatment of a non-surgical hemorrhage, the dose should be calculated as follows:

Dose (g) = [desired concentration (g/L) - basal concentration (g/L)] x 1/recovery (g/L) (g/kg) x body weight (kg),

The "1/recovery" ratio is defined by the patient's recovery (see section 5.2 of the technical data sheet), or if the recovery is unknown:

- 0.053 (g/kg)/(g/L) for children and adolescents <40 kg of body weight.

- 0.043 (g/kg)/(g/L) for adults and adolescents ≥40 kg of body weight.

Example for patient recovery and dose calculation

For a patient weighing 60 kg with a basal fibrinogen concentration of undetectable and an increase in fibrinogen to 1.20 g/L 1 hour after perfusion of 0.060 g/kg of FibCLOT:

- Calculation of patient recovery:

1.20 (g/L) / 0.060 (g/kg) = 20.0 (g/L)/(g/kg)

- Calculation of dose for an increase to 1.0 g/L:

1.0 g/L x 1 / 20.0 (g/L)/(g/kg)[or 0.050 (g/kg)/(g/L)]x 60 kg = 3 g

In case of an emergency situation where the basal fibrinogen concentration is unknown, the initial recommended dose is 0.05 g/kg of body weight administered intravenously in adults and adolescents ≥40 kg of body weight, and 0.06 g/kg of body weight in pediatric patients <40 kg of body weight.

The subsequent dosage (dose and frequency of injections) should be adapted according to the patient's clinical status and analytical results.

The biological half-life of fibrinogen is between 3 and 4 days. Therefore, if there is no consumption, it is usually not necessary to repeat treatment with human fibrinogen. Taking into account the accumulation that occurs with repeated administration for prophylactic purposes, the dose and frequency should be determined according to the therapeutic objectives of the doctor for each individual patient.

Pediatric population

The recovery and half-life in children and adolescents ≥40 kg of body weight are lower than those of adults and adolescents ≥40 kg of body weight (see section 5.2 of the technical data sheet). Therefore, adapted recoveries should be used to calculate the dose of FibCLOT in the respective body weight groups when the individual patient's recovery is unknown. It can be assumed that a body weight of <40 kg

Reconstitution:

Follow the current guidelines for aseptic procedures.

Before administering the reconstituted product, it must be visually examined to check that it does not contain particles. The reconstituted solution must be practically colorless and slightly opalescent. Do not use turbid or sediment-containing solutions.

Administration:

FibCLOT should be administered only intravenously, as a single dose, immediately after reconstitution, and at a rate not exceeding 4 mL/min.

The use of a perfusion set with a 15 µm filter, as supplied with the package, is mandatory.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

This medicinal product should not be mixed with other products and should be administered with a separate injection/perfusion catheter.