Fibryga 1 g powder and solvent for solution for injection and for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Fibryga 1g

Powder and solvent for solution for injection and for infusion

Human fibrinogen

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 pass it on to other people, 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.

Contents of the leaflet

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

1. What Fibryga is and what it is used for

Fibryga contains human fibrinogen, a protein important for blood clotting. A lack of fibrinogen means that blood does not clot as well as it should, leading to an increased tendency to bleed. Replacement of human fibrinogen with Fibryga corrects this coagulation defect.

What Fibryga is used for

Fibryga is used:

• for the treatment of bleeding episodes and surgical prophylaxis in patients with congenital fibrinogen deficiency (hypo- or afibrinogenemia) who have a tendency to bleed.
• for fibrinogen supplementation in patients with uncontrolled severe bleeding associated with acquired fibrinogen deficiency during surgery.

2. What you need to know before using Fibryga

Do not use Fibryga:

• if you are allergic to human fibrinogen or to any of the other ingredients of this medicine (listed in section 6).
• if you have previously experienced allergic reactions to Fibryga.

Please inform your doctor if you are allergic to any medication.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Fibryga.

Risk of blood clots in blood vessels

Your doctor must assess the benefits of this medicine against the risk of blood clots in blood vessels, particularly if:

• you have received a high dose or repeated doses of this medicine
• you have had a heart attack (history of coronary heart disease or myocardial infarction)
• you have liver disease
• you have recently undergone surgery (postoperative patients)
• you are about to undergo surgery (perioperative patients)
• in newborns (neonates)
• you are at risk of developing blood clots or coagulation disorders in blood vessels (patients at risk of thromboembolic events or disseminated intravascular coagulation).

Your doctor may request additional coagulation tests to monitor the risk.

Allergic and anaphylactic-type reactions

Any medicine such as Fibryga, which is prepared from human blood (containing proteins) and administered intravenously (injected into a vein), may cause allergic reactions. If you have previously experienced allergic reactions to Fibryga, your doctor will advise whether antihistamines are necessary.

Your doctor will explain the warning signs of allergic or anaphylactic-type reactions.

Please pay attention to early symptoms of allergic reactions (hypersensitivity), such as:

• rash
• skin eruption
• chest tightness
• wheezing
• hypotension,
• or anaphylaxis (when one or more of the above symptoms develop rapidly and are severe).

If such symptoms occur, the injection or infusion of Fibryga must be stopped immediately (i.e., interrupt the infusion).

Viral safety

When medicines are prepared from human blood or plasma, certain measures are taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure exclusion of those at risk of carrying infections
• testing each donation and plasma pools for signs of viruses or infections
• inclusion of steps in the processing of blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of transmitting infection cannot be completely ruled out. This also applies to any unknown or emerging viruses and other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and against the non-enveloped hepatitis A virus. The measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection may be severe in pregnant women (fetal infection) and in individuals with weakened immune systems or certain types of anemia (e.g., sickle cell anemia or abnormal breakdown of red blood cells).

It is strongly recommended that each time a dose of Fibryga is administered, the name and batch number of the product be recorded to maintain a record of batches used.

Your doctor may recommend considering vaccination against hepatitis A and B if you receive regular or repeated administration of fibrinogen products derived from human plasma.

Children and adolescents

There are no specific or additional warnings or precautions applicable to children and adolescents.

Use of Fibryga with other medicines

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

Fibryga must not be mixed with other medicines except as mentioned in the section "This information is intended for healthcare professionals only / Reconstitution".

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. This medicine should only be used during pregnancy or breastfeeding after consultation with your doctor or pharmacist.

Driving and using machines

Fibryga has no effect on the ability to drive or operate machinery.

Fibryga contains sodium

This medicine contains 132 mg of sodium (main component of table/cooking salt) per vial. This is equivalent to 6.6% of the maximum daily sodium intake recommended for an adult. Take this into account if you are following a low-sodium diet.

3. How to use Fibryga

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

Fibryga is administered as an intravenous infusion (a drip into a vein) by healthcare personnel.

The dose and dosing regimen depend on:

• your body weight
• the severity of your condition
• the site of bleeding
• the nature of your surgery, and
• your overall health status

Use in children and adolescents

The administration of Fibryga in children and adolescents (by intravenous route) does not differ from that in adults.

If you use more Fibryga than you should

To avoid the risk of overdose, your doctor will perform regular blood tests to monitor your fibrinogen levels.

In case of overdose, the risk of abnormal blood clots in blood vessels may increase.

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

Method of administration

This medicine must be injected or infused intravenously after reconstitution with the solvent supplied. If you have any further questions about the use of this product, ask your doctor or pharmacist.

4. Possible adverse effects

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

Please consult your doctor immediately:

• if any adverse effects occur
• if you notice any adverse effects not listed in this leaflet

The following adverse effects have been reported for Fibryga and other fibrinogen medicines (frequency of the listed adverse effects is unknown):

• Allergic and anaphylactic-type reactions: skin reactions such as skin rash or redness of the skin (see section 2 “Warnings and precautions”)
• Cardiovascular: inflammation of the veins and formation of blood clots (see section 2 “Warnings and precautions”)
• Increase in body temperature

If you experience any of the symptoms listed above, consult your doctor as soon as possible.

Reporting of adverse effects

If you experience any type of 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 via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Fibryga

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

Do not store above 25 °C. Do not freeze. Keep the vial in the outer packaging to protect it from light.

The powder should be dissolved only immediately before injection or infusion. The reconstituted solution has been shown to be stable for 24 hours at room temperature (maximum 25 °C). However, to avoid contamination, the solution should be used immediately and only once. The reconstituted product must not be stored in the refrigerator or freezer.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Fibryga

• The active substance is human fibrinogen.
• Fibryga contains 1 g of human fibrinogen per vial or 20 mg/ml of human fibrinogen after reconstitution with the solvent supplied (50 ml of water for injectable preparations).
• The other components are L-arginine hydrochloride, glycine, sodium chloride, and sodium citrate dihydrate.

Appearance of the product and contents of the pack

Fibryga is presented as a powder and solvent for solution for injection and for infusion, available in glass vials.

The powder is white or pale yellow, hygroscopic, and appears as a friable mass.

The solvent is a transparent, colourless liquid.

The reconstituted solution is practically colourless and slightly opalescent.

Fibryga is supplied in a box containing:

• 1 vial with powder for solution for injection and for infusion
• 1 vial with solvent (water for injectable preparations)
• 1 nextaro transfer device

Marketing Authorisation Holder

Octapharma, S.A.

Av. Castilla, 2 (P.E. San Fernando)

Ed. Dublín - 2nd Floor

28830 San Fernando de Henares

Madrid

Manufacturer

Octapharma Pharmazeutika Produktionsges.m.b.H.,

Oberlaaer Strasse 235, 1100 Vienna, Austria

or

Octapharma AB,

Lars Forssells gata 23, 112 75 Stockholm, Sweden

or

Octapharma GmbH

Elisabeth-Selbert-Str. 11, 40764 Langenfeld, Germany

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Fibryga®: Germany, Austria, Belgium, Bulgaria, Cyprus, Croatia, Denmark, Slovakia, Spain, Estonia, Finland, France, Hungary, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Netherlands, Poland, Portugal, United Kingdom (Northern Ireland), Czech Republic, Romania, Sweden

Fibrema®: Slovenia

Date of the most recent review of this summary of product characteristics: 11/2023

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended for healthcare professionals only:

Dosage

The dose and duration of replacement therapy depend on the severity of the disorder, as well as the location and extent of bleeding and the patient's clinical condition.

The fibrinogen (functional) level must be determined to calculate the individual dose, and the amount and frequency of administration should be adjusted for each patient based on regular measurement of plasma fibrinogen levels and continuous monitoring of the patient's clinical status and any other replacement therapies used.

In the case of major surgical procedures, accurate monitoring of replacement therapy using coagulation analyses is essential.

1. Prophylaxis in patients with congenital hypo- or afibrinogenemia and known bleeding tendency.

To prevent excessive bleeding during surgical procedures, prophylactic treatment is recommended to raise fibrinogen levels to 1 g/l and maintain fibrinogen at this level until haemostasis is assured, and above 0.5 g/l until wound healing is complete.

In the case of surgical procedures or treatment of a haemorrhagic episode, the dose should be calculated as follows:

Dose (mg/kg body weight) = [Target level (g/l) - measured level (g/l)] / 0.018 (g/l per mg/kg body weight)

Subsequent dosing (dose and frequency of injections) should be adjusted according to the patient's clinical condition and laboratory results.

The biological half-life of fibrinogen is 3-4 days. Therefore, in the absence of consumption, repeated administration of human fibrinogen is usually not necessary. Due to accumulation that may occur with repeated administration for prophylactic use, the dose and frequency should be determined according to the physician's therapeutic goals for each individual patient.

Paediatric population

For surgical procedures or treatment of a haemorrhagic episode, the dose in adolescents should be calculated using the formula described above for adults, whereas the dose in children <12 years of age should be calculated as follows:

Dose (mg/kg body weight) = [Target level (g/l) – measured level (g/l)] / 0.014 (g/l per mg/kg body weight)

Subsequent dosing should be adjusted according to the patient's clinical condition and laboratory results.

Elderly patients

Clinical studies with Fibryga did not include sufficient numbers of patients aged 65 years or older to determine whether they respond differently from younger patients.

1. Treatment of bleeding

Bleeding in patients with congenital hypo- or afibrinogenemia

Haemorrhagic episodes should be treated according to the formulas indicated above for adults/adolescents and children, respectively, aiming to achieve a recommended target plasma fibrinogen level of 1 g/l. This level should be maintained until haemostasis is assured.

Bleeding in patients with acquired fibrinogen deficiency

Adults

An initial dose of 1-2 g is generally administered, followed by additional infusions as needed. In cases of severe bleeding, e.g. during major surgery, higher amounts (4-8 g) of fibrinogen may be required.

Paediatric population

The dose should be determined according to body weight and clinical need, although it is typically 20-30 mg/kg.

Instructions for preparation and administration

General instructions

• The reconstituted solution should be practically colourless and slightly opalescent. Do not use cloudy solutions or those containing particles.
• Fibryga is intended for single use only. Do not reuse any of the components.
• For microbiological safety reasons, the solution should be administered immediately after reconstitution. Chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at room temperature (maximum 25 °C). After reconstitution, do not refrigerate or freeze the Fibryga solution.

Reconstitution

1. Ensure that the powder vial (Fibryga) and the solvent vial are at room temperature. This temperature should be maintained during reconstitution. If a water bath is used for warming, care must be taken to avoid contact of water with the rubber stoppers or flip-off caps of the containers. The water temperature must not exceed +37 °C.
2. Remove the flip-off caps from the powder vial (Fibryga) and the solvent vial to expose the central part of the stoppers. Clean the rubber stoppers with an alcohol swab and allow to dry.
3. Remove the lid from the transfer device (nextaro) packaging (Fig. 1). To maintain sterility, do not remove the transfer device from the transparent blister. Do not touch the spike.

1. Place the solvent vial on a clean, flat surface and hold it firmly. Without removing the blister, place the blue part of the transfer device onto the solvent vial. Press straight down firmly until it clicks into place (Fig. 2). Do not rotate when attaching.

Note: The transfer device must first be attached to the solvent vial and then to the lyophilised powder vial. Otherwise, the vacuum will be lost and solvent transfer will not occur.

1. While holding the solvent vial, carefully remove the blister from the transfer device (nextaro) by pulling it vertically upwards. Ensure that the transfer device remains securely attached to the solvent vial (Fig. 3).

1. Place the powder vial (Fibryga) on a clean, flat surface and hold it firmly. Take the solvent vial with the attached transfer device and invert it. Place the white part of the connector of the transfer device onto the powder vial (Fibryga) and press firmly down until it clicks into place (Fig. 4). Do not rotate when attaching. The solvent will automatically flow into the powder vial (Fibryga).

1. With the solvent vial still attached, gently rotate the Fibryga vial until the powder is completely dissolved. To avoid foaming, do not shake the vial. The powder should dissolve completely within approximately 5 minutes. Dissolution should not take longer than 20 minutes. If the powder has not dissolved within 20 minutes, the product must be discarded.
2. In rare cases where undissolved powder is observed floating during transfer of water for injectable preparations, or if reconstitution time is unexpectedly prolonged, dissolution may be facilitated by more vigorous horizontal shaking of the vial.
3. After reconstitution is complete, unscrew the transfer device (blue part) in two parts by turning counterclockwise (Fig. 5). Do not touch the Luer connector of the white part of the transfer device.

1. Discard the empty solvent vial together with the blue part of the transfer device.

Administration

1. Carefully attach a syringe to the Luer connector of the white part of the transfer device (Fig. 6).
2. Invert the Fibryga vial and draw the solution into the syringe (Fig. 7).

1. After transferring the solution, firmly hold the syringe barrel (with the plunger pointing downwards) and detach the syringe from the transfer device (Fig. 8).

1. Discard the white part of the transfer device together with the empty Fibryga vial.

A standard infusion set is recommended for intravenous administration of the reconstituted solution at room temperature.

Disposal of unused medicine and all materials that have been in contact with it should be carried out in accordance with local regulations.

Method of administration

Intravenous infusion or injection.

Fibryga should be administered slowly by intravenous route at a maximum recommended rate of 5 ml per minute in patients with congenital hypo- or afibrinogenemia, and at a maximum recommended rate of 10 ml per minute in patients with acquired fibrinogen deficiency.

Incompatibilities

This medicinal product must not be mixed with other medicinal products.