Product Information for the User

Willfact 500UI powder and solvent for injectable solution

Willfact 1000UIpowder and solvent for injectable solution

Willfact 2000UIpowder and solvent for injectable solution

Human von Willebrand factor

Read this entire product information carefully before starting to use this medication, because it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribedonlyto you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1.What isWillfactand what is it used for

2.What you need to know before starting touseWillfact

3.How to useWillfact

4.Possible adverse effects

5.Storage ofWillfact

6.Contents of the package and additional information

Willfactis obtained from human plasma (the liquid part of blood) andisa medication that contains the active ingredient called von Willebrand factor (VWF).

VWF is involved in blood coagulation. The lack of this factor, as occurs in von Willebrand disease, means that blood does not clot as quickly as it should, resulting in a greater tendency to bleed. Replacing VWF with Willfact will temporarily repair the blood clotting mechanisms.

Willfactis indicated for the prevention and treatment of bleedingsurgeries or of another typein patients with von Willebrand disease when treatment with desmopressin (DDAVP) alone is not effective or is contraindicated.

Willfact can be used in all age groups.

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

No useWillfact

• If you are allergic to human von Willebrand factor or any of the other components of this medication (listed in section 6).
• If you haveHemophilia A.

Warnings and precautions

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

The treatment with Willfact must always be supervised by a doctor with experience in the treatment of hemostasis disorders.

If you experience severe bleeding and a blood test indicates that the von Willebrand factor level in your blood is low, you will receive the FVW preparation in addition to a factor VIII preparation within the first 12 hours.

Allergic reactions

Like with all blood-derived or plasma-derived proteins administered intravenously, allergic reactions may occur. You will be monitored during the injection to detect any early signs of hypersensitivity. This includes, rash (hives or generalized urticaria), chest tightness, difficulty breathing, low blood pressure (hypotension), and severe allergic reactions (anaphylaxis).

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

If signs or symptoms of hypersensitivity appear, treatment should be interrupted and immediate medical attention sought.

Safety against viruses

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

• A careful selection of blood and plasma donors to ensure that those with a risk of being carriers of infections are excluded,
• Analysis of each donation and plasma groups to detect signs of viruses/infections,
• Inclusion of steps in the blood or plasma processing that may inactivate or eliminate viruses.

Despite these measures, when medications 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 adopted are considered effective for enveloped viruses, such as human immunodeficiency virus (HIV-AIDS), hepatitis B virus, and hepatitis C virus.

The measures adopted may have limited value against non-enveloped viruses, such as hepatitis A virus and parvovirus B19. Infection with parvovirus B19 can be severe for pregnant women (since there is a risk of fetal infection) and for people with immunosuppressed systems or those with 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/repeatedly receive human plasma-derived factor von Willebrand.

Batch number registration

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

Risk of thrombosis

Blood clots (thrombosis) may also obstruct blood vessels. There is a risk especially if your previous medical history or test results indicate that you have certain risk factors. In this case, you will be closely monitored to detect any early signs of thrombosis, and you will be administered preventive treatment (prophylaxis) against blood vessel obstruction due to blood clots.

When using a factor von Willebrand product that contains factor VIII, the doctor must take into account that continued treatment may produce excessive levels of FVIII. If you receive a product containing FVW, your doctor will monitor your FVIII plasma levels periodically. This ensures that sustained excessive levels of FVIII plasma levels do not occur, which could increase the risk of thrombotic events.

Limited efficacy

It is possible that, in patients with von Willebrand disease, especially patients with Type 3, proteins that neutralize the effect of FVW may form. These proteins are called neutralizing antibodies or inhibitors. If laboratory results show that your FVW levels are not being replenished or if bleeding does not stop despite administration of an adequate dose of Willfact, your doctor will check if your body has developed FVW inhibitors.

If high levels of these inhibitors are present, treatment with FVW may not be effective, and other treatment options should be considered. The new treatment will be administered by a doctor with experience in treating hemostasis disorders.

Other medications and Willfact

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

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 respect to fertility, pregnancy, and fetal development during pregnancy and after birth.

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

Driving and operating machinery

No effects have been observed on the ability to drive and operate machinery.

Willfact contains sodiumsodium

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

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

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

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

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

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

Your treatment should be initiated and monitored by a doctor with experience in the treatment of hemorrhagic disorders.

If your doctor considers that administration can be carried out in your home, they will provide you with the necessary instructions.

Dosage

Take this medicine exactly as your doctor has instructed you. If you are unsure, consult your doctor.

Preferably, Willfact should be administered by your doctor or nurse. However, if you have been prescribed Willfact to administer at home, your doctor will ensure that you are taught how to inject it and how much to use. Follow the instructions given by your doctor and ask for help if you have problems handling the syringe; it must always be used by a trained person.

Your doctor will calculate your Willfact dose (in international units or IU).

The dose you will be administered will depend on:

• Body weight,
• Location of the hemorrhage,
• Intensity of the hemorrhage,
• Clinical status,
• Surgery required,
• Levels of FVIII activity in your blood after surgery,
• Severity of your disease

This dose varies between 40 to 80 IU/kg.

Your doctor will recommend that you undergo blood tests during treatment to control:

• Factor VIII (FVIII:C) levels,
• Factor von Willebrand (FVW:Rco) levels,
• Presence of inhibitors,
• Preliminary 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 clotting protein) in addition to Willfact to treat or prevent bleeding more quickly (in emergency situations or acute bleeding).

Willfact can be administered as long-term prophylaxis; the dose level is also determined individually in this case.The doses between 40 and 60 IU/kg of Willfact, administered two or three times a week, reduce the number of hemorrhagic episodes.

Use in children and adolescents

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

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

Method of administration

The detailed instructions for reconstitution and administration of the medication are found at the end of this leaflet.

If you use moreWillfactthan you should

No symptoms of overdose have been described with Willfact.

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

If you forget to use Willfact

If you forget to take WILLFACT, consult your doctor.

Do not take a double dose to compensate for the missed dose.

If you have any other questions about the use of thismedicine, ask your doctor, pharmacist, or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

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

Get in touch with your doctor immediately if:

• You experience symptoms of hypersensitivity or allergic reactions (observed in a small number of people: may affect 1 in 100 people).

In some cases, these reactions may evolve into a severe allergic reaction (anaphylaxis) including anaphylactic shock (observed at an unknown frequency).

The warning signs of allergic reactions are

• Difficulty breathing and swallowing
• Wheezing
• Chest tightness
• Increased heart rate
• Decreased or dropped blood pressure
• Fainting
• Extreme fatigue
• Restlessness, nervousness
• Headache
• Chills, feeling cold
• Flushing, hot flashes
• Swelling in different parts of the body
• Generalized urticaria, skin rash
• Burning and itching at the infusion site
• Tickling
• Vomiting
• Nausea

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

In patients with von Willebrand disease, especially those of type 3, proteins may form that neutralize the effect of FvW. These proteins are called neutralizing antibodies or inhibitors. Patients treated with FvW should be closely monitored by their doctors to detect the appearance of inhibitors through clinical observations and appropriate laboratory tests. If such inhibitors occur, the condition may manifest as an inadequate clinical response or occur concurrently with severe allergic reactions.

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

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

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

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

• Reactions at the infusion site

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

• Dizziness
• Paresthesia, hypoesthesia
• Hot flashes
• Itching
• Sensation of oppression
• Chills, feeling cold

The following side effect has been observed at an unknown frequency:

• Fever

Reporting of 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 prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial label and the packaging.

Do not store at a temperature above + 25°C. Store in the original packaging to protect it from light.

Do not freeze.

Due to sterility reasons, the product must be used immediately after physical and chemical reconstitution. However, physical-chemical stability has been demonstrated after 24 hours at +25°C.

Do not usethis medicationif you observe that the solution is cloudy or contains deposits.

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

Composition ofWillfact

• Theactive principleis: human factor of von Willebrand (500UI, 1000 UI or 2000 UI), expressed in International Units (UI)of ristocetin cofactor activity (FVW:RCo).

After reconstitution with 5 ml (500 UI), 10 ml (1000 UI) or 20 ml (2000 UI) of water for injectable preparations, a vial contains approximately 100 UI/ml of human factor of von Willebrand.

Before adding albumin, the specific activityis greater than or equal to 60UI of FVW:RCo/mg of total protein.

• Theother componentsare:

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

Solvent:water for injectable preparations.

Aspect of the productand content of the packaging

Willfactis presented as a white or pale yellow powder or solid that can be crushed and a transparent or colorless solvent for injectable solutionafterreconstitutionwith a transfer system.

Willfact is available in 500 UI/5 ml, 1000 UI/10 ml and 2000 UI/20 ml packaging.

The reconstituted solution must be transparent or slightly opalescent, colorless or slightly yellow.

Holder of the marketing authorization

LFB-BIOMEDICAMENTS

3, avenue des Tropiques,

ZA de Courtaboeuf,

91940 Les Ulis

FRANCE

Responsible for manufacturing

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

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

LFB BIOTERAPIAS HISPANIA,S.L.

C/ Diego de León 47

28006 Madrid

(Spain)

This medication is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

AustriaWillfact

Czech RepublicWILLFACT

DenmarkWillfact

GermanyWILLFACT

HungaryWillfact

NorwayWillfact

PolandWillfact

Slovak RepublicWillfact

SpainWillfact

SwedenWillfact

United Kingdom (Northern Ireland)Willfact

Date of the last review of this leaflet:March 2024

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

_____________________________________________________________________________

INSTRUCTIONS FOR USE:

Dosage

Generally, the administration of 1 UI/kg of factor of von Willebrand raises the circulating level of FvW:RCo by approximately 0.02 UI/mL (2%).

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

Hemostasis cannot be guaranteed until the coagulant activity of factor VIII (FVIII:C) has reached 0.4 UI/ml (40%). The injection of factor of von Willebrand alone does not induce a maximum increase in FVIII:C until at least 6 to 12 hours have passed. It cannot correct the level of FVIII:C immediately. Therefore, if the patient's baseline levels of FVIII:C are below this critical level, in all situations where rapid correction of hemostasis is required, such as treatment of a hemorrhage, severe trauma or emergency surgery, factor VIII should be administered with the first injection of factor of von Willebrand to achieve a hemostatic plasma level of FVIII:C.

However, if immediate increase of FVIII:C is not required, such as in the case of scheduled surgery, or if the patient's baseline levels of FVIII:C are sufficient to ensure hemostasis, the doctor may decide to dispense with the co-administration of FVIII for the first injection of factor of von Willebrand.

• Start of treatment:

The first dose of WILLFACT is 40 to 80 UI/kg for the treatment of hemorrhages or traumas, along with the amount of factor VIII product necessary, calculated based on the patient's baseline plasma level of FVIII:C, to achieve an adequate plasma level of FVIII:C immediately before the intervention or as soon as possible after the onset of the hemorrhagic or severe traumatic episode. In the case of surgery, the first injection should be administered 1 hour before the intervention.

A dose of 80 UI/kg of WILLFACT may be necessary, especially in patients with type 3 von Willebrand disease, in whom maintaining adequate levels may require higher doses than in other types of EVW.

In the case of elective surgery, the first injection of WILLFACT should be administered between 12 and 24 hours before the intervention and the second before the same. In these cases, co-administration of a factor VIII product is not necessary, as the endogenous FVIII:C level usually reaches the critical level of 0.4 UI/mL (40%) before the intervention. However, this should be confirmed in each patient.

• Subsequent injections:

As needed, treatment should be continued with 40 to 80 UI/kg of WILLFACT alone per day, in one or two injections per day for one or several days. The dose and frequency of injections should be adapted to the type of surgical intervention, the patient's clinical and biological status (VWF:RCo and FVIII:C) and the type and severity of the hemorrhagic episode.

• Long-term prophylaxis:

WILLFACT can be administered as long-term prophylaxis, at doses adapted to each patient. Doses of WILLFACT of 40 to 60 UI/kg, administered 2 to 3 times a week, reduce the number of hemorrhagic episodes.

• Outpatient treatment:

Home treatment can be initiated with the doctor's approval, especially in cases of mild to moderate hemorrhages or during long-term prophylaxis to prevent hemorrhages.

• Pediatric population

For each indication, the dose is based on the patient's body weight. The dose and duration of treatment should be adjustedaccording to the patient's clinical status and their plasma levels of FVIII:C and FVW:Rco.

• Start of treatment:

• For children under 6years of age, the initial dose may be guided by the patient's incremental recovery (RI) or, if no RI data are available, a dose of between 60 and 100UI/kg may be necessary to elevate FVW:Rco levels to 100UI/dl.
• For children over 6years of age and adolescents, the dosage is the same as for adult patients.

• Subsequent injections:

For children and adolescents, subsequent doses should be individualized based on the patient's clinical status and FVW:Rco levels, and adjusted according to clinical response.

When there is a scheduled intervention:

• For children under 6years of age, after a first dose administered 12 to 24hours before the intervention, the repeated dose may be administered 30minutes before the intervention.
• For children over 6years of age and adolescents, the dosage is the same as for adult patients.

• Prophylaxis:

For children and adolescents, the dose and frequency of subsequent injections should be individualized based on the patient's incremental recovery and FVW:Rco levels, and adjusted according to clinical response.

Route and method of administration

Intravenous administration

Reconstitution:

Follow the current guidelines for aseptic procedures. The transfer system should only be used to reconstitute the medication, as described below. It is not designed to administer the medication to the patient.

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

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

Do not use solutions that are turbid or contain sediments.

Do not mix with other medications.

Do not dilute the reconstituted product.

Administration:

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 packaging should be carried out in accordance with local requirements.