Wilate 450

PACKAGE LEAFLET: INFORMATION FOR THE USER

Wilate 450, 450 IU FVIII/400 IU VWF, powder and solvent for solution for injection Wilate 900, 900 IU FVIII/800 IU VWF, powder and solvent for solution for injection Human coagulation factor VIII/human von Willebrand factor Read all of this leaflet carefully before you start using this medicine because it contains important information for you. • Please keep this leaflet. You may need to read it again. • If you have further questions, ask your doctor or your pharmacist. • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet:

1. What Wilate is and what it is used for

2. What you need to know before you use 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 group of medicines called clotting factors and contains human blood coagulation factor VIII and von Willebrand factor (VWF). Together these two proteins are involved in blood clotting. Von Willebrand disease Wilate is used to treat and prevent bleeding in patients with von Willebrand disease (VWD), which in fact is a family of related diseases. VWD is a disturbance of blood coagulation where bleeding can go on for longer than expected. This is either due to a lack of VWF in the blood or due to VWF that does not work the way it should. Haemophilia A Wilate is used to treat and prevent bleeding in patients with haemophilia A. This is a condition in which bleeding can go on for longer than expected. It is due to an inborn lack of factor VIII in the blood. 1/11

2. What you need to know before you use Wilate

Do not use Wilate • if you are allergic (hypersensitive) to human blood coagulation factor VIII, von Willebrand factor or any of the other ingredients of Wilate (listed in section 6). Warnings and precautions Talk to your doctor or pharmacist before using Wilate • Any medicine, such as Wilate, which is prepared from human blood (containing proteins) and which is injected into a vein (administered intravenously) can cause allergic reactions. Please pay attention to early signs of allergic reactions (hypersensitivity), such as hives, skin rash, tightness of the chest, wheezing, low blood pressure, or anaphylaxis (when any or all of the above symptoms develop rapidly and are intense). If these symptoms occur, stop the injection immediately and contact your doctor. • When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, the testing of each donation and pools of plasma for signs of virus/infections, and the inclusion of steps in the processing of the 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 passing on infection cannot be totally excluded. This also applies to any 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 the non- enveloped hepatitis A virus. The measures taken may be of limited value against non- enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (infection of the baby) and for individuals whose immune system is depressed or who have some types of anaemia (e.g. sickle cell disease or abnormal breakdown of red blood cells). • It is strongly recommended that every time you receive a dose of Wilate the name and the batch number of the product are recorded in order to maintain a record of the batches used. Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly/repeatedly receive human plasma-derived factor VIII/VWF products. Von Willebrand disease (VWD) • Please see section 4. (Von Willebrand disease (VWD)) for side effects related to the treatment of VWD. 2/11 Haemophilia A The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor VIII medicines. These inhibitors, especially at high levels, stop the treatment working properly and you or your child will be monitored carefully for the development of these inhibitors. If you or your child´s bleeding is not being controlled with Wilate, tell your doctor immediately. • Please see section 4. (Haemophilia A) for side effects related to the treatment of haemophilia A. Other medicines and Wilate Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. Although no influences on Wilate from other medicinal products are known, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines (including medicines obtained without a prescription). Please do not mix Wilate with any other medicines during the injection. Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Wilate contains sodium This medicine contains up to 58.7 mg sodium (main component of cooking/table salt) per vial for 450 IU VWF and FVIII/vial, and up to 117.3 mg per vial for 900 IU VWF and FVIII/vial. This is equivalent to 2.94%, and 5.87%, respectively, of the recommended maximum daily dietary intake of sodium for an adult.

3. How to use Wilate

Wilate should be injected into a vein (administered intravenously) after reconstitution with the supplied solvent. Treatment should be started under medical control. Dosage Your doctor will advise you about your individual dosage and the frequency with which you should use Wilate. Always use Wilate exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. If you use more Wilate than you should No symptoms of overdose with human factor VIII or VWF have been reported. However, the recommended dosage should not be exceeded. If you forget to take Wilate Do not take a double dosage to make up for a forgotten dosage. 3/11 If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medicines, Wilate can cause side effects, although not everybody gets them. • Hypersensitivity or allergic reactions have been commonly observed. These may include: burning and stinging at the infusion site, chills, flushing, headache, hives (urticaria), low blood pressure (hypotension), tiredness (lethargy), sickness (nausea), restlessness, increase of heart rate (tachycardia), tightness of the chest, feeling of pins and needles (tingling), vomiting, wheezing, sudden swellings in various parts of the body (angiooedema). If you suffer from any of the above-mentioned symptoms, please inform your doctor. You should stop using Wilate and see your doctor immediately, if you experience symptoms of angiooedema, such as: o swollen face, tongue or throat (pharynx) o difficulties to swallow o hives and difficulties to breath • Fever has also been commonly observed. • Even though uncommon, dizziness has also been observed. • Abdominal pain, back pain, chest pain and cough 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 any or all of the above symptoms develop rapidly and are intense), which may include shock. In case of an anaphylactic shock, treatment using the current medical recommendations for shock is essential. Von Willebrand disease (VWD) • When using a factor VIII-containing VWF product to treat VWD, the continued treatment may cause an excessive rise in factor VIII in the blood. This may increase the risk that your blood flow will be disturbed (thrombosis). If you are a patient with known clinical or laboratory risk factors, you have to be checked for early signs of thrombosis. Prevention (prophylaxis) of thrombotic events should be decided by your doctor, according to the current recommendations. • Patients with VWD (especially type 3 patients) may develop inhibitors (neutralising antibodies) to VWF during the treatment with VWF. In these very rare cases inhibitors can stop Wilate working properly. In case your bleeding continues, your blood has to be tested for these inhibitors. 4/11 Inhibitors may increase the risk of suffering severe allergic reactions (anaphylactic shock). If you suffer an allergic reaction, you should be tested for the presence of inhibitors. Once inhibitors have been found in your blood, please contact a physician with experience in the care of patients with bleeding disorders. In patients with high amounts of inhibitors, another kind of treatment might be useful and should be considered. Haemophilia A • For children not previously treated with factor VIII medicines, inhibitor antibodies (see section 2) may form very commonly (more than 1 in 10 patients); however patients who have received previous treatment with factor VIII (more than 150 days of treatment) the risk is uncommon (less than 1 in 100 patients). If this happens you or your child´s medicines may stop working properly and you or your child may experience persistent bleeding. If this happens, you should contact your doctor immediately. Inhibitors may increase the risk of suffering severe allergic reactions (anaphylactic shock). If you suffer an allergic reaction, you should be tested for the presence of inhibitors. Common: may affect up to 1 in 10 people Uncommon: may affect up to 1 in 100 people Rare: may affect up to 1 in 1,000 people Very rare: may affect up to 1 in 10,000 people There are insufficient data to recommend the use of Wilate in previously untreated patients. The experience of treatment with Wilate in children less than 6 years of age is limited. For information on viral safety see section 2. (Warnings and precautions). Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V* – [to be completed nationally]. 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 the sight and reach of children. Store powder and solvent vial in a refrigerator (2°C – 8°C). Do not freeze. Keep the vials in the outer carton in order to protect from light. 5/11 Do not use Wilate after the expiry date stated on the label. Wilate can be stored at room temperature (max. +25°C) for 2 months. In this case the shelf-life expires 2 months after the product has been taken out of the refrigerator for the first time. The new shelf-life has to be noted on the outer carton by you. The powder should be dissolved only directly before injection. The stability of the solution has been demonstrated for 4 hours at room temperature. Nevertheless, to prevent contamination, the solution should be used immediately and on one occasion only. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Wilate contains − The active substances are human coagulation factor VIII and human von Willebrand factor − The other ingredients are sodium chloride, glycine, sucrose, sodium citrate and calcium chloride. Solvent: water for injections with 0.1% Polysorbate 80 What Wilate looks like and contents of the pack Freeze-dried powder: white or pale yellow powder or crumbly solid Reconstituted solution: should be clear or slightly opalescent Wilate is supplied as a powder and solvent for solution for injection. It comes in 2 pack sizes: • Wilate 450, 450 IU FVIII and 400 IU VWF, powder and solvent for solution for injection, contains nominally 450 IU human coagulation factor VIII and 400 IU human von Willebrand factor per vial. The product contains approximately 90 IU/ml human coagulation factor VIII and 80 IU/ml human von Willebrand factor when reconstituted with 5 ml of Water for Injections with 0.1% Polysorbate 80 (Solvent). • Wilate 900, 900 IU FVIII and 800 IU VWF, powder and solvent for solution for injection, contains nominally 900 IU human coagulation factor VIII and 800 IU human von Willebrand factor per vial. The product contains approximately 90 IU/ml human coagulation factor VIII and 80 IU/ml human von Willebrand factor when reconstituted with 10 ml of Water for Injections with 0.1% Polysorbate 80 (Solvent). Content of the package 1 vial with freeze-dried powder 1 vial with solvent 1 equipment pack for intravenous injection (1 transfer set, 1 infusion set, 1 disposable syringe) 2 alcohol swabs Marketing Authorisation Holder and Manufacturer 6/11 {to be completed nationally} For any further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder: {to be completed nationally} Manufacturer Octapharma Pharmazeutika Produktionsges.m.b.H. Oberlaaerstr. 235 A-1100 Vienna Austria Octapharma Dessau GmbH Otto-Reuter-Str. 3 D-06847 Dessau-Roßlau Germany This leaflet was last approved in . 7/11 Instructions for Home Treatment • Please read all the instructions and follow them carefully! • Do not use Wilate after expiry date given on the label. • During the procedure described below, sterility must be maintained! • Reconstituted medicinal product should be inspected visually for particulate matter and discoloration prior to administration. • The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or have deposits. • Use the prepared solution immediately, to prevent microbial contamination. • Only use the infusion set provided. The use of other injection/infusion equipment can cause additional risks and treatment failure. Instructions for Preparing the Solution: 1. Do not use the product directly from the refrigerator. Allow the solvent and the powder in the 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 transfer set is depicted in Fig. 1. Place the solvent vial on an even surface and hold it firmly. Take the transfer set and turn it upside down. Place the blue part of the transfer set on top of the solvent vial and press firmly down until it snaps (Fig. 2 + 3). Do not twist while attaching. Powder adapter (white part) Solvent adapter (blue part) Fig. 1 Fig. 2 Fig. 3 8/11

4. Place the powder vial on an even surface and hold it

firmly. Take the solvent vial with the attached transfer set and turn it upside down. Place the white part on top of the powder vial and press firmly down until it snaps (Fig. 4). Do not twist while attaching. The solvent flows automatically into the powder vial. Fig. 4

5. With both vials still attached, gently swirl the powder

vial until the product is dissolved. The dissolving is completed in less than 10 minutes at room temperature. Slight foaming might occur during preparation. Unscrew the transfer set into two parts (Fig. 5). Foaming will disappear. Dispose the empty solvent vial together with the blue part of the transfer set. Fig. 5 9/11 Instructions for Injection: As a precaution, your pulse rate should be taken before and during the injection. If a marked increase in your pulse rate occurs, reduce the injection speed or interrupt the administration for a short time. 1. Attach the syringe to the white part of the transfer set. Turn the vial upside down and draw the solution into the syringe (Fig. 6). The solution should be clear or slightly opalescent. Once the solution has been transferred, firmly hold the plunger of the syringe (keeping it facing down) and remove the syringe from the transfer set (Fig. 7). Dispose the empty vial together with the white part of the transfer set. Fig. 6 Fig. 7

2. Clean the chosen injection site with one of the provided alcohol swabs

3. Attach the provided infusion set to the syringe.

4. Insert the injection needle into the chosen vein. If you have used a tourniquet to make the vein easier to see, this tourniquet should be released before you start injecting Wilate. No blood must flow into the syringe due to the risk of formation of fibrin clots. 5. Inject the solution into the vein at a slow speed, not faster than 2-3 ml per minute in patients weighing 10 kg or more. For patients weighing between 6 kg and less than 10 kg, the infusion rate should not exceed 2 ml per minute. For patients weighing less than 6 kg, the infusion rate should not exceed 1 ml per minute. If you use more than one vial of Wilate powder for one treatment, you may use the same injection needle and syringe again. The transfer set is for single use only. 10/11 Any unused product or waste material should be disposed of in accordance with local requirements. Wilate must not be mixed or injected (with the same infusion set) with other medicinal products. Only use the infusion set provided. The use of other injection/infusion equipment can cause additional risks and treatment failure (factor VIII/VWF adsorption to the internal surfaces of some infusion equipment). 11/11