Willfact 1000 IU powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Willfact 500IU powder and solvent for solution for injection

Willfact 1000IU powder and solvent for solution for injection

Willfact 2000IU powder and solvent for solution for injection

human von Willebrand factor

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

• Keep this leaflet. 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. It may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet:

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

1. What Willfact is and what it is used for

Willfact is obtained from human plasma (the liquid part of blood) and is a medicine containing the active substance called von Willebrand factor (VWF).

VWF plays a role in blood clotting. A deficiency of this factor, as occurs in von Willebrand disease, means that blood does not clot as quickly as it should, resulting in an increased tendency to bleed. Replacement of VWF with Willfact will temporarily correct the blood clotting mechanisms.

Willfact is indicated for the prevention and treatment of surgical or other bleeding in patients with von Wille游戏副本land disease when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.

Willfact can be used in all age groups.

Willfact should not be used as a treatment for Hemophilia A.

2. What you need to know before using Willfact

Do not use Willfact

• if you are allergic to human von Willebrand factor or to any of the other components of this medicine (listed in section 6).
• if you have Haemophilia A.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Willfact.

Treatment with Willfact must always be supervised by a physician experienced in the treatment of coagulation disorders.

If you experience severe bleeding and a blood test shows low factor VIII levels, you will receive the von Willebrand factor (VWF) preparation together with a factor VIII preparation within the first 12 hours.

Allergic reactions

As with all intravenously administered proteins derived from human blood or plasma, hypersensitivity reactions in the form of allergy may occur. During the infusion, you will be monitored for any early signs of hypersensitivity. These include rash (hives or generalized urticaria), chest tightness, difficulty breathing, low blood pressure (hypotension), and severe allergic reactions (anaphylaxis).

Your doctor will inform you about the warning signs of an allergic reaction.

If signs or symptoms of hypersensitivity occur, treatment must be stopped immediately and medical attention must be sought urgently.

Virus safety

When medicines are made from human blood or plasma, certain measures are taken to prevent the 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 of each donation and plasma pools for signs of viruses/infections,
• Inclusion of processing steps 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 or other types of infections.

The measures taken are considered effective against enveloped viruses, such as the human immunodeficiency virus (HIV/AIDS), hepatitis B virus, and hepatitis C virus.

The measures taken may have limited effectiveness against non-enveloped viruses, such as hepatitis A virus and parvovirus B19. Parvovirus B19 infection may be serious in pregnant women (due to the risk of fetal infection) and in individuals with weakened immune systems or certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).

Vaccinations

Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly or repeatedly receive von Willebrand factor derived from human plasma.

Batch number registration

It is strongly recommended that each time you receive a dose of Willfact, the name and batch number of the medicine be recorded to maintain a record of the batches used.

Thrombosis risk

Blood clots (thrombosis) can also block blood vessels. The risk is especially high if your medical history or laboratory results indicate certain risk factors. In such cases, you will be closely monitored for any early signs of thrombosis, and you may require preventive treatment (prophylaxis) against venous obstruction due to blood clots.

When using a von Willebrand factor product containing factor VIII, your doctor must consider that prolonged treatment may lead to excessive increases in factor VIII levels. If you receive a VWF product containing factor VIII, your doctor will periodically monitor your plasma factor VIII levels. This ensures that sustained elevated plasma factor VIII levels do not occur, which could increase the risk of thrombotic events.

Limited efficacy

In patients with von Willebrand disease, especially those with Type 3, it is possible that the body may produce proteins that neutralize the effect of VWF. These proteins are called neutralizing antibodies or inhibitors. If laboratory results show that your VWF levels are not increasing or if bleeding does not stop despite administration of an adequate dose of Willfact, your doctor will check whether your body has developed VWF inhibitors.

If these inhibitors are present at high concentrations, treatment with VWF may not be effective, and alternative treatment options should be considered. Any new treatment will be administered by a physician experienced in managing coagulation disorders.

Other medicines and Willfact

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

Pregnancy and breastfeeding

Willfact should not be used during pregnancy or breastfeeding unless clearly indicated.

The safety of Willfact during pregnancy and breastfeeding has not been studied in controlled clinical trials. Animal studies are insufficient to establish safety with regard to fertility, pregnancy, and child development during pregnancy and after birth.

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

Driving and using machines

No effects on the ability to drive or use machines have been observed.

Willfact contains sodium

A 5 ml vial (500 IU) of Willfact contains 0.15 mmol (3.4 mg) of sodium.

This corresponds to 0.17% of the maximum daily recommended sodium intake for an adult.

A 10 ml vial (1000 IU) of Willfact contains 0.3 mmol (6.9 mg) of sodium.

This corresponds to 0.35% of the maximum daily recommended sodium intake for an adult.

A 20 ml vial (2000 IU) of Willfact contains 0.6 mmol (13.8 mg) of sodium.

This corresponds to 0.69% of the maximum daily recommended sodium intake for an adult.

3. How to use Willfact

Your treatment should be initiated and monitored by a physician experienced in the management of bleeding disorders.

If your doctor considers that administration can be performed at home, appropriate instructions will be provided to you.

Posology

Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.

Ideally, Willfact should be administered by your doctor or nurse. However, if your doctor has prescribed Willfact for self-administration at home, your doctor will ensure that you are trained in how to inject it and in the correct dosage to use. Follow your doctor's instructions carefully and seek help if you have difficulty handling the syringe; the syringe must always be used by a trained individual.

Your doctor will calculate your Willfact dose (in International Units or IU).

Your dose will depend on:

• Body weight,
• Site of bleeding,
• Severity of bleeding,
• Clinical condition,
• Required surgery,
• von Willebrand factor (VWF) activity levels in your blood after surgery,
• Severity of your condition.

This dose ranges between 40 and 80 IU/kg.

Your doctor will recommend regular blood tests during treatment to monitor:

• Factor VIII levels (FVIII:C),
• von Willebrand factor levels (VWF:RCo),
• Presence of inhibitors,
• Early signs of clot formation if you are at risk of such complications.

Based on the results of these tests, your doctor may decide to adjust the dose and frequency of your injections.

In certain cases, it may be necessary to use a factor VIII preparation (another coagulation protein) in addition to Willfact to more rapidly treat or prevent bleeding (in emergency situations or acute bleeding episodes).

Willfact may be used for long-term prophylaxis; in this case, the dose level is also individually determined. Doses of 40 to 60 IU/kg of Willfact administered two or three times per week reduce the number of bleeding episodes.

Use in children and adolescents

The dose for children and adolescents is based on body weight. In some cases, particularly in younger patients (under 6 years of age), higher doses (up to 100 IU/kg) may be required.

Inform your doctor if you think that the effect of Willfact is too strong or too weak.

Method of administration

Detailed instructions for reconstitution and administration of the medicine are provided at the end of this leaflet.

If you use more Willfact than you should

Symptoms of overdose with Willfact have not been reported.

However, the risk of thrombosis cannot be ruled out in the case of significant overdosage.

If you forget to use Willfact

If you forget to take WILLFACT, consult your doctor.

Do not take a double dose to make up for the missed dose.

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

Contact your doctor immediately if:

• You notice symptoms of hypersensitivity or allergic reactions (seen uncommonly: may affect up to 1 in 100 people).

In some cases, these reactions may progress to a severe allergic reaction (anaphylaxis), including anaphylactic shock (frequency unknown).

Warning signs of allergic reactions include:

• Difficulty breathing and swallowing
• Wheezing
• Chest tightness
• Increased heart rate
• Decrease or drop in blood pressure
• Fainting
• Extreme fatigue
• Restlessness, nervousness
• Headache
• Chills, feeling cold
• Flushing, hot flashes
• Swelling in different parts of the body
• Skin rash, generalized hives
• Burning and stinging at the infusion site
• Tingling
• Vomiting
• Nausea

If any of these effects occur, stop treatment immediately and contact your doctor to initiate appropriate treatment depending on the type and severity of the reaction.

• Notice that the medicine stops working properly (bleeding is not controlled). This may be due to inhibition of von Willebrand factor (observed with unknown frequency).

In patients with von Willebrand disease, especially those with type 3, proteins may form that neutralize the effect of VWF. These proteins are called neutralizing antibodies or inhibitors. Patients treated with VWF should be carefully monitored by their physicians for the development of inhibitors through clinical observations and appropriate laboratory tests. If such inhibitors develop, the condition may present as an inadequate clinical response or may occur concomitantly with severe allergic reactions.

• Notice any symptoms of impaired perfusion in the limbs (e.g., cold and pale extremities) or in vital organs (e.g., severe chest pain). This may be due to formation of blood clots in blood vessels (observed with unknown frequency).

There is a risk of blood clot formation (thrombosis), especially in patients with known risk factors. After correction of von Willebrand factor deficiency, patients should be monitored for early signs of thrombosis or disseminated intravascular coagulation and should receive treatment to prevent thrombosis in situations involving an increased risk of thrombosis (after surgery, during bed rest, in cases of deficiency of a coagulation inhibitor or a fibrinolytic enzyme).

If you receive FVIII preparations containing VWF, the risk of thrombosis may also increase due to persistently elevated plasma levels of FVIII.

The following adverse reaction has been frequently observed (may affect up to 1 in 10 people):

• Reactions at the infusion site

The following adverse reactions have been observed infrequently (may affect up to 1 in 100 people):

• Dizziness
• Paresthesia, hypoesthesia
• Flushing
• Itching
• Sensation of tightness
• Chills, feeling cold

The following adverse reaction has been observed with unknown frequency:

• Fever

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Willfact

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

Do not use this medicine after the expiry date stated on the vial label and outer packaging.

Do not store above +25°C. Store in the original container to protect from light.

Do not freeze.

For sterility reasons, the product should be used immediately after physical and chemical reconstitution. However, physicochemical stability has been demonstrated for up to 24 hours at +25°C.

Do not use this medicine if you notice that the solution is cloudy or contains particles.

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

6. Contents of the pack and other information

Composition of Willfact

• The active substance is: human von Willebrand factor (500 IU, 1000 IU or 2000 IU), expressed in International Units (IU) of ristocetin cofactor activity (VWF:RCo).

After reconstitution with 5 mL (500 IU), 10 mL (1000 IU) or 20 mL (2000 IU) of water for injections, a vial contains approximately 100 IU/mL of human von Willebrand factor.

Before addition of albumin, the specific activity is greater than or equal to 60 IU of VWF:RCo/mg of total protein.

• The other components are:

Powder: human albumin, arginine hydrochloride, glycine, sodium citrate and calcium chloride dihydrate.

Solvent: water for injections.

Nature of the product and contents of the container

Willfact is presented as a white or pale yellow powder or friable solid and a transparent or colourless solvent for reconstitution into an injectable solution using a transfer system.

Willfact is available in pack sizes of 500 IU/5 mL, 1000 IU/10 mL and 2000 IU/20 mL.

The reconstituted solution should be transparent or slightly opalescent, colourless or slightly yellow.

Marketing Authorisation Holder

LFB-BIOMEDICAMENTS

3, avenue des Tropiques,

ZA de Courtaboeuf,

91940 Les Ulis

FRANCE

Manufacturer

LFB BIOMEDICAMENTS

3, Avenue des Tropiques, BP 305 - Les Ulis, Courtaboeuf - F-91958 – France

or

LFB BIOMEDICAMENTS

59 Rue de Trevise. BP 2006 - Lille - F-59011 - France

Further information on this medicinal product is available from the local representative of the Marketing Authorisation Holder:

LFB BIOTERAPIAS HISPANIA, S.L.

C/ Diego de León 47

28006 Madrid

(Spain)

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

Austria Willfact

Czech Republic WILLFACT

Denmark Willfact

Germany WILLFACT

Hungary Willfact

Norway Willfact

Poland Willfact

Slovak Republic Willfact

Spain Willfact

Sweden Willfact

United Kingdom (Northern Ireland) Willfact

Date of the most recent revision of this leaflet: March 2024

Detailed and up-to-date 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/

_____________________________________________________________________________

INSTRUCTIONS FOR USE:

Dosage

In general, administration of 1 IU/kg of von Willebrand factor increases circulating VWF:RCo levels by approximately 0.02 IU/mL (2%).

Target levels of VWF:RCo > 0.6 IU/mL (60%) and FVIII:C > 0.4 IU/mL (40%) should be achieved.

Haemostasis cannot be ensured until factor VIII coagulant activity (FVIII:C) has reached 0.4 IU/mL (40%). Injection of von Willebrand factor alone does not induce a maximal increase in FVIII:C until at least 6 to 12 hours have passed. It cannot immediately correct FVIII:C levels. Therefore, when the patient's basal FVIII:C levels are below this critical threshold and rapid correction of haemostasis is required—such as in the treatment of bleeding, major trauma, or emergency surgery—factor VIII must be administered together with the first dose of von Willebrand factor to achieve a haemostatic plasma level of FVIII:C.

However, if an immediate increase in FVIII:C is not required, as in the case of scheduled surgery, or if the patient's basal FVIII:C levels are sufficient to ensure haemostasis, the physician may decide not to co-administer FVIII with the first dose of von Willebrand factor.

• Initiation of treatment:

The initial dose of WILLFACT is 40 to 80 IU/kg for the treatment of bleeding or trauma, together with the necessary amount of factor VIII product, calculated based on the patient's basal plasma FVIII:C level, in order to achieve an adequate haemostatic plasma level of FVIII:C immediately before surgery or as soon as possible after the onset of a bleeding episode or major trauma. In the case of surgery, the first dose should be administered 1 hour before the procedure.

An initial dose of 80 IU/kg of WILLFACT may be required, especially in patients with type 3 von Willebrand disease, in whom maintaining adequate levels may require higher doses than in other types of VWD.

In the case of elective surgery, the first dose of WILLFACT should be administered between 12 and 24 hours before surgery, and the second dose before the procedure. In these cases, concomitant administration of factor VIII product is not necessary, as endogenous FVIII:C usually reaches the critical level of 0.4 IU/mL (40%) before surgery. However, this must be confirmed for each individual patient.

• Subsequent injections:

If necessary, treatment should continue with 40 to 80 IU/kg of WILLFACT alone per day, administered in one or two daily infusions for one or several days. The dose and frequency of infusions should always be adjusted according to the type of surgical procedure, the patient's clinical and biological status (VWF:RCo and FVIII:C), and the type and severity of the bleeding episode.

• Long-term prophylaxis:

WILLFACT may be administered as long-term prophylaxis, with doses adjusted to the individual patient. Doses of WILLFACT of 40 to 60 IU/kg administered 2 to 3 times per week reduce the number of bleeding episodes.

• Outpatient treatment:

Home treatment may be initiated with the approval of the physician, particularly in cases of mild to moderate bleeding episodes or during long-term prophylaxis to prevent bleeding.

• Paediatric population

For each indication, the dose is based on body weight. The dose and duration of treatment should be adjusted according to the patient's clinical condition and plasma levels of FVIII:C and VWF:RCo.

• Initiation of treatment:

• For patients under 6 years of age, the initial dose may be guided by the patient's incremental recovery (IR), or, if IR data are not available, an initial dose of 60 to 100 IU/kg may be required to raise VWF:RCo levels to 100 IU/dL.

• For children over 6 years of age and adolescents, the dosing regimen is the same as for adult patients.

• Subsequent injections:

For children and adolescents, subsequent doses should be individualised according to clinical status and VWF:RCo levels, and adjusted based on clinical response.

When a scheduled surgical procedure is planned:

• For patients under 6 years of age, after an initial dose administered 12 to 24 hours before surgery, a repeat dose may be given 30 minutes before the procedure.

• For children over 6 years of age and adolescents, the dosing regimen is the same as for adult patients.

• Prophylaxis:

For children and adolescents, the dose and frequency of subsequent administrations should be individualised based on the patient's incremental recovery and VWF:RCo levels, and adjusted according to clinical response.

Route and method of administration

Intravenous administration

Reconstitution:

Current guidelines for aseptic procedures must be followed. The transfer system is intended solely for reconstituting the medicinal product as described below and is not designed to administer the product to the patient.

Allow both vials (powder and solvent) to reach a temperature not exceeding 25°C. Remove the protective caps from the solvent vial (water for injectable preparations) and the powder vial. Disinfect the surface of each stopper. Remove the cap from the Mix2Vial device. Without removing the device from its packaging, attach the blue end of the Mix2Vial to the solvent vial stopper. Remove and discard the packaging. Be careful not to touch the now-exposed part of the device. Invert the solvent vial with the attached device and connect it to the powder vial using the transparent end of the device. The solvent will automatically transfer into the powder vial. Hold the assembly and gently shake to completely dissolve the product. Next, hold the reconstituted product vial with one hand and the solvent vial with the other, then unscrew the Mix2Vial device to separate the vials.

The powder usually dissolves instantly and should dissolve within less than 10 minutes.

The solution should be clear or slightly opalescent, colorless or pale yellow. The reconstituted product should be inspected visually for particles and discoloration prior to administration.

Do not use solutions that are cloudy or contain precipitates.

Do not mix with other medicines.

Do not dilute the reconstituted product.

Administration:

Hold the vial of reconstituted product in an upright position while screwing the sterile syringe onto the Mix2Vial device. Then, slowly draw the product into the syringe. Once the product has been transferred to the syringe, firmly hold the syringe (keeping the plunger downward), unscrew the Mix2Vial device, and replace it with a butterfly or intravenous needle. Remove air from the syringe and insert it into the vein after disinfecting the skin surface. Administer slowly by intravenous injection as a single dose immediately after reconstitution, at a maximum rate of 4 ml/minute.

Storage after reconstitution

For reasons of sterility, the product should be used immediately after reconstitution. However, its physical and chemical stability has been demonstrated for 24 hours at +25°C.

Disposal of unused products or containers must be carried out in accordance with local requirements.