Wilate

PACKAGE LEAFLET: INFORMATION FOR THE USER

Wilate “500 IU VWF / 500 IU FVIII - powder and solvent for injectable solution”, “1000 IU VWF / 1000 IU FVIII - powder and solvent for injectable solution”

Human von Willebrand factor / human coagulation factor VIII
Please read this leaflet carefully before you use 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Wilate is and what it is used for

Wilate belongs to the pharmacotherapeutic category of medicines known as coagulation factors and contains von Willebrand Factor (VWF) and human blood coagulation Factor VIII.
These proteins are involved together in blood clotting.

von Willebrand Disease
Wilate is used to treat and prevent bleeding in patients with von Willebrand disease (VWD), which is actually a group of related disorders. von Willebrand disease is a blood clotting disorder in which bleeding may last longer than expected. This is due to a lack of VWF in the blood or to VWF that does not function properly.

Haemophilia A
Wilate is used to treat and prevent bleeding in patients with haemophilia A. This is a condition in which bleeding may continue for a longer time than expected. The cause is a congenital deficiency of Factor VIII in the blood.

2. What you should know before using Wilate

Do not use Wilate
If you are allergic (hypersensitive) to von Willebrand factor or coagulation factor VIII of human
origin, or to any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Tell your doctor or pharmacist before using Wilate

• Any medicine, such as Wilate, prepared from human blood (containing proteins) and injected into a vein (administered intravenously) may cause allergic reactions. Please pay attention to the first signs of allergic reactions (hypersensitivity), such as hives, skin rash, chest tightness, wheezing, drop in blood pressure, or anaphylaxis (when one or all of the above symptoms develop rapidly and are severe). If these symptoms occur, stop administration immediately and contact your doctor.
• When medicines are produced from human blood or plasma, standard measures are taken to prevent infections being transmitted to patients. These measures include careful selection of blood and plasma donors to ensure exclusion of those at risk of transmitting infections, testing of each donation and plasma pools for viruses/infections, and inclusion of processing steps capable of inactivating or removing viruses. Despite these measures, when medicines derived from human blood or plasma are administered, the possibility of transmission of infectious agents cannot be completely ruled out. This applies also to 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, as well as against the non-enveloped hepatitis A virus. These measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be severe in pregnant women (infection of the fetus) and in individuals with compromised immune systems or certain forms of anaemia (such as sickle cell anaemia or abnormal red blood cell metabolism). It is strongly recommended that each time you receive a dose of Wilate, the name and batch number of the product are recorded in order to maintain a record of the batches used. Your doctor may recommend considering vaccination against hepatitis A and B, especially if you receive regular/repeated treatments with VWF/factor VIII products derived from human plasma.

Von Willebrand disease (VWD)

• Please see Section 4. (Von Willebrand disease (VWD)) for treatment-related adverse reactions associated with VWD treatment.

Haemophilia A
The development of inhibitors (antibodies) is a known complication that may occur during treatment
with all factor VIII-containing medicines. Inhibitors, especially at high levels, prevent the treatment from working properly, and you or your child will be closely monitored for the development of such inhibitors. If Wilate does not control the bleeding in you or your child, inform your doctor immediately.

• Please see Section 4. (Haemophilia A) for treatment-related adverse reactions associated with Haemophilia A treatment.

Other medicines and Wilate
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines.
Although no interactions with Wilate from other medicines are known, inform your doctor or
pharmacist if you are taking or have recently taken other medicines (including those without
prescription).
It is recommended not to mix Wilate with any other medicine during injection.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding,
please consult your doctor or pharmacist before using this medicine.
Wilate contains sodium
This medicine contains up to 58.7 mg of sodium (a main component of table salt) per vial in the 500 IU vial of VWF and FVIII, and up to 117.3 mg of sodium per vial in the 1000 IU vial of VWF and FVIII. This corresponds to 2.94% and 5.87% respectively of the maximum daily recommended dietary intake of sodium for an adult.

3. How to use WILATE

WILATE must be administered intravenously (by intravenous injection) after reconstitution with the solvent provided. Treatment must be initiated under medical supervision.
Dosage
Your doctor will inform you about your individual dosage and how often you should use Wilate.
Always use Wilate exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
If you use more Wilate than you should
Symptoms of overdose with VWF or human factor VIII have not been reported. However, the recommended dose must not be exceeded.
If you forget to take Wilate
Do not take a double dose to make up for a missed dose.
If you have any doubts about the use of this medicinal product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Wilate can cause side effects, although not everybody gets them.

• Although not common, hypersensitivity or allergic reactions have been observed. These may include: burning and stinging pain at the infusion site, chills, flushing, headache, itching (urticaria), low blood pressure (hypotension), tiredness (lethargy), discomfort (nausea), restlessness, increased heart rate (tachycardia), chest tightness, sensation of pins and needles (tingling), vomiting, wheezing, sudden swelling in various parts of the body (angioedema). If you experience any of the symptoms listed above, inform your doctor.

You must stop administering Wilate immediately and contact your doctor right away if you
experience symptoms of angioedema such as:

swelling of the face, tongue or throat (pharynx)
difficulty swallowing
hives and difficulty breathing

• Although not common, fever has been observed.
• Abdominal pain, back pain, chest pain, cough and dizziness may also occur, but the frequency of these side effects is unknown.
• In very rare cases, hypersensitivity may lead to a severe allergic reaction called anaphylaxis (when one or both of the above symptoms develop rapidly and are intense), which may lead to shock. In case of anaphylactic shock, specific treatment according to current medical guidelines for shock management is essential. Von Willebrand Disease (VWD)
• When using a VWF-containing product with factor VIII for the treatment of VWD, continued treatment may cause excessive increase of factor VIII in the blood. This may increase the risk of disturbances in blood flow (thrombosis). If you are a patient with known clinical or laboratory risk factors, you should be monitored for early signs of thrombosis. Prevention (prophylaxis) of thrombotic events should be decided by your doctor according to current recommendations.
• Patients with von Willebrand disease (especially those with type 3) may develop inhibitors (neutralizing antibodies) to VWF during treatment with VWF. In these very rare cases, inhibitors may prevent Wilate from working properly. If bleeding continues, your blood should be tested for these inhibitors.

Inhibitors may increase the risk of developing severe allergic reactions (anaphylactic shock). If an allergic reaction occurs, you should undergo testing to determine the presence of inhibitors.
If inhibitors are detected in your blood, it is recommended that you consult a doctor experienced in treating patients with coagulation disorders. In patients with high inhibitor levels, another type of treatment may be beneficial and should be considered.
Haemophilia A

• In children who have not previously been treated with factor VIII-containing medicines, the development of inhibitory antibodies (see section 2) may be very common (more than 1 in 10 patients); however, in patients who have received prior treatment with factor VIII (more than 150 exposure days), the risk is not common (less than 1 in 100 patients). If this occurs, the medicine may no longer work properly and you or your child may experience persistent bleeding. If this happens, contact your doctor immediately. Inhibitors may increase the risk of developing severe allergic reactions (anaphylactic shock). If you experience allergic reactions, you should undergo testing to check for the presence of inhibitors. Not common: affects up to 1 in 100 people Rare: affects up to 1 in 1,000 people Very rare: affects up to 1 in 10,000 people. There are insufficient data to recommend the use of Wilate in previously untreated patients. Experience with Wilate in children under 6 years of age is limited. For information on viral safety, see section 2 (Warnings and precautions).

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store WILATE

Keep this medicine out of sight and reach of children.
Store the vials of powder and solvent in a refrigerator (2°C–8°C).
Do not freeze.
Keep the vials in the outer packaging to protect them from light.
Do not use Wilate after the expiry date stated on the label.
Wilate may be stored at room temperature (not above 25°C) for up to 2 months. In this case,
the product's shelf life expires 2 months after it has first been removed from the refrigerator.
Record the new expiry date on the outer packaging.
The powder should only be dissolved immediately before injection. The stability of the solution has been demonstrated for 4 hours at room temperature. However, to avoid contamination, the solution should be used immediately and only once.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Wilate contains

• The active substances are human von Willebrand factor and human coagulation factor VIII.
• The excipients are: sodium chloride, glycine, sucrose, sodium citrate, and calcium chloride. Solvent: water for injectable preparations with 0.1% polysorbate 80.

Description of the appearance of Wilate and contents of the pack
Lyophilisate in powder form: white or slightly yellowish, friable powder or solid.
Reconstituted solution: should be clear or slightly opalescent.
Wilate is supplied as a powder and solvent for injectable solution.
It is available in two pack sizes:

• Wilate 500, 500 IU of VWF and 500 IU of FVIII, powder and solvent for injectable solution. Each vial contains nominally 500 IU of human VW factor and 500 IU of human coagulation factor VIII. The product contains approximately 100 IU/ml of human VW factor and 100 IU/ml of human coagulation factor VIII after reconstitution with 5 ml of water for injectable preparations with 0.1% polysorbate 80 (solvent).
• Wilate 1000, 1000 IU of VWF and 1000 IU of FVIII, powder and solvent for injectable solution. Each vial contains nominally 1000 IU of human VW factor and 1000 IU of human coagulation factor VIII. The product contains approximately 100 IU/ml of human VW factor and 100 IU/ml of human coagulation factor VIII after reconstitution with 10 ml of water for injectable preparations with 0.1% polysorbate 80 (solvent).

Contents of the pack
1 vial of lyophilized powder
1 vial of solvent
1 package containing the following medical devices:
1 single-use syringe
1 transfer device (Mix2Vial)
1 infusion device
2 alcohol swabs

Marketing Authorization Holder and Manufacturer
OCTAPHARMA ITALY S.p.A.
Via Cisanello 145 - 56124 PISA - Italy
For any further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder.

Manufacturers responsible for batch release
Octapharma Pharmazeutika
Produktionsges.m.b.H.
Oberlaaerstr. 235
A-1100 Vienna
Austria

This patient information leaflet was last approved on: 02/2020
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovenia, Slovakia, Spain, United Kingdom: Wilate 500 / Wilate 1000
Finland, Norway, Sweden: Wilate
Denmark: Wilnativ
France: Eqwilate 500 / Eqwilate 1000

Instructions for home treatment

• Please read all instructions carefully and follow them precisely!
• Do not use Wilate after the expiry date stated on the label.
• Sterility must be maintained throughout the procedure described below.
• The reconstituted medicine should be inspected visually for the presence of particles or discoloration before administration.
• The solution in the syringe must be clear or slightly opalescent. Do not use solutions that are cloudy or contain deposits.
• Use the prepared solution immediately to avoid microbial contamination.
• Use only the injection set provided. Using other injection/infusion devices may cause additional risks and treatment failure.

Instructions for preparing the solution:

1. Do not use the product immediately after removing it from the refrigerator. Allow the solvent and powder in their closed vials to reach room temperature.
2. Remove the flip-off caps from both vials and clean the rubber stoppers with one of the provided alcohol swabs.
3. The Mix2Vial is shown in Fig. 1:

Place the solvent vial on a flat surface and hold it firmly.
Take the Mix2Vial and turn it upside down.
Place the blue part of the Mix2Vial onto the top of the solvent vial and press firmly downward until it locks into place (Fig. 2 + 3).

4. Place the powder vial on a flat surface and hold it firmly. Take the solvent vial attached to the Mix2Vial and turn it upside down. Place the transparent part onto the top of the powder vial and press firmly downward until it locks into place (Fig. 4). The solvent will automatically transfer into the powder vial.

5. With both vials still connected, gently invert the powder vial until the product is fully dissolved. Dissolution takes less than 10 minutes at room temperature. A slight foam may form during reconstitution.

Unscrew the Mix2Vial into two parts (Fig. 5).
The foam will disappear.
Dispose of the empty solvent vial together with the blue part of the Mix2Vial.

Instructions for injection:
As a precaution, heart rate should be monitored before and during injection. If a marked increase in heart rate occurs, reduce the injection rate or temporarily interrupt administration.

1. Attach the syringe to the transparent part of the Mix2Vial. Turn the vial upside down and draw the solution into the syringe (Fig. 6).

The solution in the syringe must be clear or slightly pearly.
Once the solution has been transferred, hold the syringe plunger firmly (with the plunger facing downward) and remove the syringe from the Mix2Vial (Fig. 7).
Dispose of the Mix2Vial and the empty vial.

2. Clean the selected injection site with one of the provided alcohol swabs.
3. Attach the provided injection needle to the syringe.
4. Insert the injection needle into the selected vein. If a tourniquet has been used to make the vein more visible, it must be released before starting the injection of Wilate. Blood must not flow back into the syringe due to the risk of fibrin clot formation.
5. Inject the solution intravenously slowly, at a rate no faster than 2–3 ml per minute. If more than one vial of Wilate powder is used for a single treatment, the same needle and syringe may be reused. The Mix2Vial is for single use only.

Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.
Wilate must not be mixed or co-administered (using the same infusion set) with other medicinal products.
Use only the infusion set specifically provided.
The use of another injection/infusion device may result in an increased risk of treatment failure (due to adsorption of VWF/factor VIII onto the internal surfaces of certain infusion devices).