PROSPECTO: INFORMATION FOR THE USER

WILATE,500UIFvWand 500 UI FVIII, powder and solvent for injectable solution.

WILATE,1000UIFvWand 1000 UI FVIII, powder and solvent for injectable solution.

Human von Willebrand factor and human coagulation factor VIII.

6.Contents of the package and additional information

Wilate belongs to the pharmacotherapeutic group of medications known as coagulation factors, contains human von Willebrand factor (FvW) and human coagulation factor VIII.

These two proteins together intervene in blood coagulation.

Von Willebrand disease

Wilate is used to treat and prevent bleeding in patients with von Willebrand disease (VWD), which is a group of related disorders.The VWD is a blood coagulation anomaly by which a bleeding may last longer than expected.This may be due to a lack of FvW in the blood or that the FvW does not function as it should.

Hemophilia A

Wilate is used to treat and prevent bleeding in patients with hemophilia A. This is a disease in which bleeding may last longer than expected. It is due to an innate lack of factor VIII in the blood.

No use Wilate

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

Warnings and precautions

Consult your doctor or pharmacist before starting to use Wilate.

• Any medication, like Wilate, that is prepared from human blood (containing proteins) and injected into a vein (administered intravenously) may cause allergic reactions. Be aware of the first signs of allergic reactions (hypersensitivity), such as urticaria, skin rash, chest tightness, difficulty breathing, low blood pressure, or anaphylaxis (when any of the above or all of them develop rapidly and are intense).

If you experience these symptoms, stop the injection immediately and contact your doctor.

• When administering medications derived from plasma or human blood, certain measures must be taken to prevent infections from being transmitted to patients.These measures include a careful selection of blood and plasma donors to ensure the exclusion of those at risk of being carriers of infections, analysis of virus/infection signs in individual donations and plasma mixtures, as well as the inclusion of stages in the blood or plasma processing capable of inactivating or eliminating viruses.Despite these measures, when administering medications prepared from human blood or plasma, the possibility of transmission of infection cannot be entirely ruled out. This also applies to all unknown or emerging viruses or other types of infections.

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

Parvovirus B19 infection can be severe for a pregnant woman (infection in the baby) and for people with a weakened immune system or those with some type of anemia (e.g., hemolytic anemia or abnormal destruction of red blood cells).

• It is strongly recommended that each time you receive a dose of Wilate, you note the name and batch number of the product in order to maintain a record of the batches used.

Your doctor may recommend that you be vaccinated against hepatitis A and B if you are regularly/repeatedly administered human plasma-derived FvW/factor VIII products.

Von Willebrand Disease (VWD)

• See section 4. (Von Willebrand Disease (VWD) for side effects related to VWD treatment.

Hemophilia A

The formation of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII medications. These inhibitors, especially in large quantities, prevent the treatment from working properly, so you and your child will be closely monitored for the development of these inhibitors. If your bleeding or your child's bleeding is not being controlled with Wilate, consult your doctor immediately.

• See section 4. (Hemophilia A) for side effects related to hemophilia A treatment.

Use of Wilate with other medications

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

Although no interactions of Wilate with other medications are known, inform your doctor or pharmacist if you are using or have used recently other medications, even those obtained without a prescription.

Do not mix Wilate with other medications during the injection.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before using any medication.

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

Wilate contains sodium

This medication contains up to 58.7 mg of sodium (main component of table salt/for cooking) in each 500 UI FvW and FVIII vial and up to 117.3 mg in each 1000 UI FvW and FVIII vial. This corresponds to 2.94% and 5.87%, respectively, of the recommended daily maximum sodium intake for an adult.

Wilate must be injected into a vein (administered intravenously) after reconstitution with the provided solvent. Treatment should be initiated under medical supervision.

Dose

Your doctor will recommend your individual dose and the frequency at which you should use Wilate. Follow exactly the administration instructions for Wilate indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

If you use more Wilate than you should

No adverse effects of overdose with FvW or human factor VIII have been described. However, do not exceed the recommended dose.

If you forgot to use Wilate

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

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

Like all medicines, Wilate may cause side effects, although not everyone will experience them.

• Although infrequently, hypersensitivity or allergic reactions have been observed. These reactions may include:

redness and itching at the injection site, chills, hot flushes, headache, rashes (urticaria), decreased blood pressure (hypotension), fatigue (lethargy), dizziness (nausea), restlessness, increased heart rate (tachycardia), chest tightness, prickling (paresthesia), vomiting, breathing difficulty, sudden swelling in various parts of the body (angioedema).

If you experience any of the symptoms mentioned above, inform your doctor.

You must discontinue use of Wilate and see your doctor immediately if you experience symptoms of angioedema, such as:

• swollen face, tongue, or throat (pharynx)
• difficulty swallowing
• urticaria and difficulty breathing

• Although infrequently, fever has also been observed.
• Dyspepsia, back pain, chest pain, cough, and dizziness may also occur, but the frequency of these adverse reactions is unknown.
• In rare cases, hypersensitivity may lead to a severe allergic reaction called anaphylaxis (when any of the above symptoms or all of them develop rapidly and are intense), which may include shock. In the event of anaphylactic shock, essential treatment using current medical guidelines for shock is required.

Von Willebrand Disease (VWD)

• When using a VWF product containing factor VIII to treat VWD, continued treatment may cause an excessive increase in factor VIII in the blood. This may increase the risk of altered blood flow (thrombosis).

If you are a patient with known clinical or laboratory risk factors, your doctor must monitor the first signs of thrombosis. Your doctor should establish a prevention (prophylaxis) of thrombotic episodes, in accordance with current recommendations.

• Patients with VWD (especially type 3 patients) may develop inhibitors (neutralizing antibodies) to VWF during treatment with VWF. In these rare cases, the inhibitors may interrupt the proper functioning of Wilate.

In the event of continued bleeding, the presence of these inhibitors in your blood must be analyzed.

Inhibitors may increase the risk of severe allergic reactions (anaphylactic shock). If you experience an allergic reaction, the presence of inhibitors must be analyzed.

Once inhibitors have been detected in your blood, contact a doctor experienced in the care of patients with bleeding disorders. In patients with high levels of inhibitors, alternative treatment may be useful and should be considered.

Hemophilia A

• In children who have not received prior treatment with factor VIII-containing medications, inhibitors (see section 2) may occur very frequently (more than 1 in 10 patients); however, in patients who have received prior treatment with factor VIII (more than 150 days of treatment), the risk is infrequent (less than 1 in 100 patients). If this occurs, the medications you or your child take may not work properly, and you or your child may experience persistent bleeding. In this case, contact your doctor immediately.

Inhibitors may increase the risk of severe allergic reactions (anaphylactic shock). If you experience an allergic reaction, the presence of inhibitors must be analyzed.

There are insufficient data to recommend the use of Wilate in untreated patients.

The experience of treating Wilate in children under 6 years of age is limited.

For information on viral safety, see section 2 (Warnings and precautions).

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 can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

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

Store the powder and vial of solvent in the refrigerator (2°C- 8°C).

Do not freeze.

Store the vials in the outer packaging to protect them from light.

Do not use Wilate after the expiration date that appears on the packaging afterCad: The expiration date is the last day of the month indicated.

Wilate can be stored at a temperature below25ºCfor 2 months. In this case, the validity period is 2 months after the product has been removed from the refrigerator for the first time. You must note the new validity period on the box.

The powder should only be dissolved immediately before injection. The solution has been shown to be stable for 4 hours at a temperature below25ºC. However, to avoid contamination, the solution should be used immediately and only once.Medicines should not be thrown away through drains or in the trash. Ask your pharmacisthow to dispose ofthepackaging and themedicines that you no longerneed.By doing so, you will help protect the environment.

Composition of Wilate

• The active principle is human von Willebrand factor and human coagulation factor VIII.
• The other components are sodium chloride, glycine, sucrose, sodium citrate, calcium chloride. Solvent: water for injection with 0.1% polisorbate 80.

Appearance of the product and contents of the package

Lyophilized powder: white or pale yellow or solid powder.

Reconstituted solution: it must be transparent or slightly opalescent.

Wilate is supplied as a powder and a solvent for injectable solution. It is presented in 2 package sizes:

• Wilate, 500 UI FvW and 500 UI FVIII, powder and solvent for injectable solution, contains nominally 500 UI of human von Willebrand factor and 500 UI of human coagulation factor VIII per vial. The product contains approximately 100 UI/ml of human von Willebrand factor and 100 UI/ml of human coagulation factor VIII when reconstituted with 5 ml of water for injection with a 0.1% polisorbate 80 (solvent).
• Wilate, 1000 UI FvW and 1000 UI FVIII, powder and solvent for injectable solution, contains nominally 1000 UI of human von Willebrand factor and 1000 UI of human coagulation factor VIII per vial. The product contains approximately 100 UI/ml of human von Willebrand factor and 100 UI/ml of human coagulation factor VIII when reconstituted with 10 ml of water for injection with a 0.1% polisorbate 80 (solvent).

Contents of the package

1 vial of lyophilized powder

1 vial of solvent

1 box with the intravenous injection equipment (1 transfer set, 1 infusion set, 1 disposable syringe)

2 alcohol wipes

Marketing authorization holder and responsible manufacturer

Octapharma S.A

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

Ed. Dublin – 2nd Floor, 28830 San Fernando de Henares

Madrid

Responsible manufacturer:

Octapharma Dessau GmbH

Otto-Reuter-Str. 3

D-06847 Dessau-Roßlau

Germany

u

Octapharma Pharmazeutika Produktionsges.m.b.H.

Oberlaaerstr.235

A-1100 Vienna

Austria

u

Octapharma GmbH

Elisabeth-Selberst-Str. 11

40764 Langenfeld

Germany

Last review date of this leaflet: 02/2021

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

Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovenia, Slovak Republic, Spain, United Kingdom:Wilate 500/Wilate 1000

Finland, Norway, Sweden:Wilate

Denmark:Wilnativ

France:Eqwilate 500/ Eqwilate 1000

Instructions for outpatient treatment

• Read all instructions and follow them carefully.
• Do not use Wilate after the expiration date that appears on the package.
• During the procedure described below, maintain sterility.
• The reconstituted solution must be visually inspected to detect particles or color changes before administration.
• The solution must be clear or slightly opalescent. Do not use turbid or sediment-containing solutions.

• Use the solution immediately after preparation, to avoid microbial contamination.
• Use only the equipment provided. The use of other injection/infusion equipment may cause additional risks and treatment failure.

Instructions for preparing the solution:

1. Do not use the product directly from the refrigerator. Leave the solvent and powder in the closed vials until they reach room temperature.
2. Remove the flip-off caps from the vials and clean the rubber stoppers with one of the alcohol wipes provided.
3. The transfer set is represented in Fig. 1. Place the solvent vial on a flat surface and hold it firmly in place. Take the transfer set and turn it over. Place the blue part of the transfer set on top of the solvent vial and press firmly until you hear a click (Fig. 2 + 3). Do not turn it while attaching.

Instructions for injection:

As a precaution, measure your pulse rate before and during injection. If your pulse rate increases significantly, reduce the injection rate or interrupt administration for a brief period.

1. Attach the syringe to the white part of the transfer set. Turn the vial over and draw the solution into the syringe (Fig.6). The solution must be clear or slightly opalescent.
   Once the solution has been transferred, hold the syringe plunger firmly in place (keeping it down) and remove the syringe from the transfer set (Fig. 7). Discard the empty vial along with the white part of the transfer set.

1. Clean the area where the injection will be given with one of the alcohol wipes provided.

3.Attach the infusion set provided to the syringe.

1. Insert the injection needle into the selected vein. If you have used a tourniquet to make the vein more visible, this tourniquet must be released before starting to inject Wilate.

No blood should flow into the syringe due to the risk of fibrin clot formation.

1. Inject the solution into the vein at a slow rate, not exceeding 2-3 ml per minute.

If you use more than one vial of Wilate powder for treatment, you can use the same injection needle and syringe. The transfer set is for single use.

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

Wilate should not be mixed or injected (with the same infusion set) with other medications. Use only the infusion set provided. The use of other injection/infusion equipment may cause additional risks and treatment failure (adsorption of FvW/factor VIII on the internal surfaces of some infusion sets).

The detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/